Current treatments for postmenopausal osteoporosis
suffer from side effects. Safe and natural milk
proteins, ribonuclease, and lactoferrin promote formation
of new capillaries and bone formation.
This study investigated the effects of a ribonuclease-enriched lactoferrin (R-ELF) supplement on bone turnover markers in 38 postmenopausal women over 6 months. The women were randomized to receive either R-ELF capsules twice daily plus calcium or a placebo of calcium alone. Bone resorption markers decreased and bone formation markers increased more in the R-ELF group compared to the placebo group. Specifically, R-ELF demonstrated a 14% decrease in urine deoxypyridinoline levels and maintenance of serum N-telopeptide levels at 24% of baseline, while placebo showed a 19% and 41% increase respectively. R-ELF also showed a 45% increase in bone-specific
Bone is a dynamic tissue that is continuously renewed through the process of bone remodeling. This process is carried out by basic multicellular units containing osteoclasts, which resorb bone, and osteoblasts, which form new bone. A normal bone remodeling cycle maintains bone mass and quality through a balanced relationship between bone resorption and formation. Dysfunctions in osteoclasts or osteoblasts can disrupt this balance and lead to metabolic bone diseases characterized by either high or low bone turnover.
This document discusses various medications approved for treating osteoporosis. It describes bisphosphonates, which decrease bone loss by inhibiting osteoclasts, as well as selective estrogen receptor modulators like raloxifene. Strontium ranelate, teriparatide, and calcitonin are also outlined as they increase bone formation or decrease resorption. New drugs under investigation include denosumab, romosozumab, and ostabolin-cyclic PTH1-35 which aim to reduce fractures by novel mechanisms of bone formation or resorption inhibition.
This document summarizes current and newer therapies for osteoporosis. It describes the FDA-approved pharmacologic options including bisphosphonates, estrogens, raloxifene, calcitonin, parathyroid hormone, and denosumab. It then discusses the efficacy of these current treatments in reducing vertebral and non-vertebral fractures. The document notes the need for newer agents due to safety concerns with long-term bisphosphonate use. It introduces several promising new therapies in development including denosumab, anti-sclerostin antibodies, and cathepsin K inhibitors which have shown increases in bone mineral density and reductions in fracture risk in clinical trials.
Recent advances in osteoporosis new copyDr Sourya M
Osteoporosis is characterized by low bone mass and deterioration of bone structure, making bones fragile and prone to fractures. Key drugs used to treat osteoporosis include calcium, vitamin D, bisphosphonates, SERMs, calcitonin, PTH and teriparatide, and denosumab. Newer drugs under development include romosozumab, a sclerostin inhibitor that strongly increases bone mineral density, abaloparatide, and integrin antagonists. Non-drug approaches also show promise such as biomaterials and gut serotonin inhibitors.
This document discusses osteoporosis management and the efficacy and safety of bisphosphonates. It begins with an overview of the burden of osteoporosis, noting that over 2.5 million people in Indonesia have osteoporosis and over 88 million have osteopenia. It then reviews screening and treatment guidelines before focusing on bisphosphonates. The document discusses the efficacy of various bisphosphonates at reducing fractures based on clinical trials. It also reviews controversial issues associated with long-term bisphosphonate use such as osteonecrosis of the jaw, atypical fractures, atrial fibrillation, and esophageal cancer. It concludes by noting that annual zoledronic acid injections can significantly reduce hip,
The document discusses drug-induced osteoporosis, focusing on glucocorticoids, aromatase inhibitors, androgen deprivation therapy, Depo-provera, proton pump inhibitors, and selective serotonin reuptake inhibitors. It summarizes their effects on bone loss and fracture risk, mechanisms of action, and treatment approaches. Key findings include rapid bone loss associated with glucocorticoid use, increased fracture risk from aromatase inhibitors and androgen deprivation therapy for cancer patients, and conflicting data on fracture risk from proton pump inhibitor use.
This study investigated the effects of a ribonuclease-enriched lactoferrin (R-ELF) supplement on bone turnover markers in 38 postmenopausal women over 6 months. The women were randomized to receive either R-ELF capsules twice daily plus calcium or a placebo of calcium alone. Bone resorption markers decreased and bone formation markers increased more in the R-ELF group compared to the placebo group. Specifically, R-ELF demonstrated a 14% decrease in urine deoxypyridinoline levels and maintenance of serum N-telopeptide levels at 24% of baseline, while placebo showed a 19% and 41% increase respectively. R-ELF also showed a 45% increase in bone-specific
Bone is a dynamic tissue that is continuously renewed through the process of bone remodeling. This process is carried out by basic multicellular units containing osteoclasts, which resorb bone, and osteoblasts, which form new bone. A normal bone remodeling cycle maintains bone mass and quality through a balanced relationship between bone resorption and formation. Dysfunctions in osteoclasts or osteoblasts can disrupt this balance and lead to metabolic bone diseases characterized by either high or low bone turnover.
This document discusses various medications approved for treating osteoporosis. It describes bisphosphonates, which decrease bone loss by inhibiting osteoclasts, as well as selective estrogen receptor modulators like raloxifene. Strontium ranelate, teriparatide, and calcitonin are also outlined as they increase bone formation or decrease resorption. New drugs under investigation include denosumab, romosozumab, and ostabolin-cyclic PTH1-35 which aim to reduce fractures by novel mechanisms of bone formation or resorption inhibition.
This document summarizes current and newer therapies for osteoporosis. It describes the FDA-approved pharmacologic options including bisphosphonates, estrogens, raloxifene, calcitonin, parathyroid hormone, and denosumab. It then discusses the efficacy of these current treatments in reducing vertebral and non-vertebral fractures. The document notes the need for newer agents due to safety concerns with long-term bisphosphonate use. It introduces several promising new therapies in development including denosumab, anti-sclerostin antibodies, and cathepsin K inhibitors which have shown increases in bone mineral density and reductions in fracture risk in clinical trials.
Recent advances in osteoporosis new copyDr Sourya M
Osteoporosis is characterized by low bone mass and deterioration of bone structure, making bones fragile and prone to fractures. Key drugs used to treat osteoporosis include calcium, vitamin D, bisphosphonates, SERMs, calcitonin, PTH and teriparatide, and denosumab. Newer drugs under development include romosozumab, a sclerostin inhibitor that strongly increases bone mineral density, abaloparatide, and integrin antagonists. Non-drug approaches also show promise such as biomaterials and gut serotonin inhibitors.
This document discusses osteoporosis management and the efficacy and safety of bisphosphonates. It begins with an overview of the burden of osteoporosis, noting that over 2.5 million people in Indonesia have osteoporosis and over 88 million have osteopenia. It then reviews screening and treatment guidelines before focusing on bisphosphonates. The document discusses the efficacy of various bisphosphonates at reducing fractures based on clinical trials. It also reviews controversial issues associated with long-term bisphosphonate use such as osteonecrosis of the jaw, atypical fractures, atrial fibrillation, and esophageal cancer. It concludes by noting that annual zoledronic acid injections can significantly reduce hip,
The document discusses drug-induced osteoporosis, focusing on glucocorticoids, aromatase inhibitors, androgen deprivation therapy, Depo-provera, proton pump inhibitors, and selective serotonin reuptake inhibitors. It summarizes their effects on bone loss and fracture risk, mechanisms of action, and treatment approaches. Key findings include rapid bone loss associated with glucocorticoid use, increased fracture risk from aromatase inhibitors and androgen deprivation therapy for cancer patients, and conflicting data on fracture risk from proton pump inhibitor use.
osteoporosis for more details comment and contactshifanishifani
This document discusses osteoporosis and metabolic bone diseases. It provides definitions and key concepts, including that bone densitometry can determine bone mass and predict fracture risk. It discusses epidemiology of osteoporosis, bone physiology including remodeling, and factors influencing bone health such as vitamin D, calcium, and hormones. Risk factors for osteoporosis include aging, hormonal changes, nutrition, lifestyle, disease states, and medications. Low bone density increases fracture risk and can result from failure to reach peak bone mass or accelerated bone loss later in life.
Bisphosphonates are commonly used to treat bone metastases from cancers like breast, lung and prostate cancer. They work by inhibiting osteoclast activity and bone resorption, thereby reducing complications from bone metastases like fractures, bone pain and hypercalcemia. The document recommends bisphosphonates like zoledronate and pamidronate for reducing skeletal complications in patients with osteolytic bone tumors, multiple myeloma, hypercalcemia or those receiving aromatase inhibitor therapy. It provides guidance on screening patients, choosing agents, administration, monitoring side effects and treatment cycles.
Prof. Jon Tobias's presentation from Osteoporosis 2016: What are the properties of the perfect therapy?
Find out more at: https://nos.org.uk/conference
1) Inhibition of bone formation plays a crucial role in the pathogenesis of glucocorticoid-induced osteoporosis (GIOP).
2) Bone loss is much larger in patients starting glucocorticoid treatment than in those on chronic treatment.
3) Lifestyle measures like calcium, vitamin D, exercise, and fall prevention are important for preventing fractures in GIOP.
This document discusses metabolic bone diseases, including their composition, calcium and phosphate metabolism, and specific diseases. It provides details on osteoporosis, rickets/osteomalacia, Paget's disease, and renal osteodystrophy. The composition of bone includes collagen, proteoglycans, and hydroxyapatite. Calcium and vitamin D intake recommendations are outlined for different populations. PTH, calcitonin, vitamin D, and alkaline phosphatase roles in calcium regulation are summarized. Osteoporosis risk factors and management strategies are highlighted.
This document provides an overview of bone structure, function, composition, and disease. It discusses bone proteins including collagen, biomarkers of bone formation like BAP and osteocalcin, and resorption like CTX. Bone metabolism involves calcium, phosphate, PTH, and vitamin D. Osteoporosis results from imbalanced bone turnover. Therapies aim to reduce resorption with bisphosphonates or HRT, or stimulate formation with PTH or growth factors. Biomarkers like BAP and CTX can monitor therapy response by detecting changes within months.
Osteoporosis is caused by estrogen deficiency after menopause. It leads to reduced bone density and increased fracture risk. Over 50% of postmenopausal women suffer osteoporotic fractures. Risk factors include advancing age, family history, smoking, excessive alcohol, low body weight and falls. Diagnosis involves testing for bone mineral density loss using DXA scanning or calculating fracture risk with FRAX. Prevention focuses on exercise, nutrition, fall prevention and medications. Cardiovascular disease risk rises after menopause due to declines in estrogen and HDL cholesterol and increases in blood pressure and LDL cholesterol. Risk is assessed through history, exams and testing to determine prevention strategies. While estrogen was thought to benefit brain function,
This document provides an overview of bisphosphonates including their history, chemical structure, types, mechanism of action, uses, administration, and potential side effects like BRONJ. Some key points:
- Bisphosphonates are a class of drugs that prevent bone loss and are used to treat bone metastases, osteoporosis, and Paget's disease.
- They have a high affinity for hydroxyapatite crystals in bone and inhibit osteoclast activity and bone resorption.
- Nitrogen-containing bisphosphonates are more potent than early non-nitrogenous versions. Mechanisms of action differ between the two classes.
- While bisphosphonates showed
This document discusses metabolic bone diseases. It begins by describing the basic structure and function of bone, including its cellular components like osteoblasts and osteoclasts. It then discusses the constituents of bone matrix, including collagen, proteoglycans, and minerals. Bone development and homeostasis are explained, involving processes like remodeling. Specific metabolic bone diseases are then outlined in more detail, including osteogenesis imperfecta (brittle bone disease), osteomalacia/rickets due to abnormal mineralization, and hypophosphatasia due to a genetic disturbance in alkaline phosphatase synthesis. Throughout, the document provides microscopic and radiographic characteristics of these conditions.
Vitamin D plays an important role in muscle function and strength. Low vitamin D levels are associated with sarcopenia, or the loss of muscle mass and strength that occurs with aging. A study of over 800 men found that lower vitamin D levels were a significant determinant of lower relative appendicular skeletal muscle mass, even after adjusting for other factors. Another study of nearly 1,000 older adults found that lower vitamin D levels were associated with poorer performance on physical tests of mobility and strength. Maintaining adequate vitamin D levels may help reduce the risk of sarcopenia and falls in older adults.
Nutrition interventions for frailty and sarcopeniaMary Hickson
Nutritional interventions that may help combat sarcopenia and frailty include protein, essential amino acids, vitamin D, and antioxidants. While protein supplementation shows some promise, the evidence is inconsistent due to variations in study design and populations. Essential amino acid and vitamin D supplementation appear to improve muscle mass and strength, especially in deficient individuals, but more research is still needed. Overall, the evidence suggests protein and vitamin D have the most potential to treat and prevent sarcopenia, but better designed studies are required to provide definitive conclusions.
Bisphosphonates are a class of drugs that prevent bone loss and are used to treat bone metastases, osteoporosis, and Paget's disease. They have a high affinity for hydroxyapatite crystals in bone and work by inhibiting bone resorption. There are two types - non-nitrogenous bisphosphonates which induce osteoclast apoptosis, and nitrogenous bisphosphonates which inhibit protein prenylation in osteoclasts. Common indications include postmenopausal osteoporosis, glucocorticoid-induced osteoporosis, and bone metastases. While generally well-tolerated, side effects can include upset stomach, esophagus problems, and osteonecrosis of the
Muscle mass and strength decrease with age, known as sarcopenia. By age 75, sedentary adults can lose up to 30% of muscle mass. This contributes to chronic diseases and loss of physical function and independence. Resistance training and adequate protein intake can help prevent or reverse age-related muscle loss. While older adults can regain strength after training, they may have smaller gains in muscle size compared to younger adults due to diminished muscle regeneration ability with aging.
Optimizing Medical Nutrition Therapy in sarcopenia of Elderly patients Chomarhlaing
The document discusses optimizing medical nutrition therapy for sarcopenia in elderly patients. It defines sarcopenia as the loss of skeletal muscle mass and strength that occurs with aging. The prevalence of sarcopenia increases with age, affecting 5-13% of 60-70 year olds and 11-50% of those over 80. Consequences of sarcopenia include physical impairment, falls, disability and mortality. Screening tools like SARC-F can help diagnose sarcopenia based on measures of muscle mass, strength and physical performance. Management involves exercise programs and medical nutrition therapy, with a focus on adequate protein intake, particularly high-quality proteins containing amino acids like leucine, arginine and glutamine.
Presented by Linus Lay, Pharm.D. Candidate from the University of Rhode Island Class of 2022.
This presentation is on behalf of the Hackettstown Medical Center Pharmacy at Hackettstown, New Jersey as part of Continuing Education.
The Osteoporosis Overview goes over a brief introduction to osteoporosis and current/updated treatment guidelines based on global usage, drug effectiveness, and American association of clinical endocrinologists.
View MyCred Portfolio: https://mycred.com/p/2929377185
Biochemical tests are used to diagnose bone diseases. Serum tests measure calcium, phosphate, alkaline phosphatase, parathyroid hormone, and vitamin D levels. Urine tests measure calcium, phosphate, and bone turnover markers. Common bone diseases include arthritis, osteoporosis, rickets/osteomalacia, and Paget's disease. Arthritis causes joint symptoms. Osteoporosis weakens bones and increases fracture risk. Rickets/osteomalacia cause soft bones from vitamin D deficiency. Paget's disease involves abnormal bone remodeling.
Use of bisphosphonates in orthopaedic surgeryLove2jaipal
Bisphosphonates are a class of drugs used to treat bone disorders involving increased bone resorption. They work by inhibiting osteoclast activity and bone resorption. There are several generations of bisphosphonates with varying potencies, and they have many orthopedic indications including osteoporosis, bone metastases, and Paget's disease. Bisphosphonates have been shown to effectively reduce fracture risk in osteoporosis trials and decrease mortality in elderly patients at high risk for fracture. While generally well-tolerated, they can cause side effects including upset stomach and joint pain.
Cultured milk is fermented milk made using lactic acid bacteria cultures which gives it a longer shelf life of 4 days compared to 24 hours for fresh pasteurized milk. It is more digestible, providing better nutrition. Cultured milk can help those who experience stomach upset from fresh milk, and regular consumption has therapeutic properties. It can be consumed by everyone as its probiotics regulate bowel movements and maintain intestinal bacterial balance while reducing toxin production in the body.
The article is about different types of milk that can be consumed, including milk from cows, goats, sheep, and reindeer. Milk is healthy and used to make dairy products like yogurt, sour cream, and cheese. Cheese is popular because there are many varieties that differ in shape, size, and taste. Some people cannot consume dairy products or drink milk because they are allergic to it.
osteoporosis for more details comment and contactshifanishifani
This document discusses osteoporosis and metabolic bone diseases. It provides definitions and key concepts, including that bone densitometry can determine bone mass and predict fracture risk. It discusses epidemiology of osteoporosis, bone physiology including remodeling, and factors influencing bone health such as vitamin D, calcium, and hormones. Risk factors for osteoporosis include aging, hormonal changes, nutrition, lifestyle, disease states, and medications. Low bone density increases fracture risk and can result from failure to reach peak bone mass or accelerated bone loss later in life.
Bisphosphonates are commonly used to treat bone metastases from cancers like breast, lung and prostate cancer. They work by inhibiting osteoclast activity and bone resorption, thereby reducing complications from bone metastases like fractures, bone pain and hypercalcemia. The document recommends bisphosphonates like zoledronate and pamidronate for reducing skeletal complications in patients with osteolytic bone tumors, multiple myeloma, hypercalcemia or those receiving aromatase inhibitor therapy. It provides guidance on screening patients, choosing agents, administration, monitoring side effects and treatment cycles.
Prof. Jon Tobias's presentation from Osteoporosis 2016: What are the properties of the perfect therapy?
Find out more at: https://nos.org.uk/conference
1) Inhibition of bone formation plays a crucial role in the pathogenesis of glucocorticoid-induced osteoporosis (GIOP).
2) Bone loss is much larger in patients starting glucocorticoid treatment than in those on chronic treatment.
3) Lifestyle measures like calcium, vitamin D, exercise, and fall prevention are important for preventing fractures in GIOP.
This document discusses metabolic bone diseases, including their composition, calcium and phosphate metabolism, and specific diseases. It provides details on osteoporosis, rickets/osteomalacia, Paget's disease, and renal osteodystrophy. The composition of bone includes collagen, proteoglycans, and hydroxyapatite. Calcium and vitamin D intake recommendations are outlined for different populations. PTH, calcitonin, vitamin D, and alkaline phosphatase roles in calcium regulation are summarized. Osteoporosis risk factors and management strategies are highlighted.
This document provides an overview of bone structure, function, composition, and disease. It discusses bone proteins including collagen, biomarkers of bone formation like BAP and osteocalcin, and resorption like CTX. Bone metabolism involves calcium, phosphate, PTH, and vitamin D. Osteoporosis results from imbalanced bone turnover. Therapies aim to reduce resorption with bisphosphonates or HRT, or stimulate formation with PTH or growth factors. Biomarkers like BAP and CTX can monitor therapy response by detecting changes within months.
Osteoporosis is caused by estrogen deficiency after menopause. It leads to reduced bone density and increased fracture risk. Over 50% of postmenopausal women suffer osteoporotic fractures. Risk factors include advancing age, family history, smoking, excessive alcohol, low body weight and falls. Diagnosis involves testing for bone mineral density loss using DXA scanning or calculating fracture risk with FRAX. Prevention focuses on exercise, nutrition, fall prevention and medications. Cardiovascular disease risk rises after menopause due to declines in estrogen and HDL cholesterol and increases in blood pressure and LDL cholesterol. Risk is assessed through history, exams and testing to determine prevention strategies. While estrogen was thought to benefit brain function,
This document provides an overview of bisphosphonates including their history, chemical structure, types, mechanism of action, uses, administration, and potential side effects like BRONJ. Some key points:
- Bisphosphonates are a class of drugs that prevent bone loss and are used to treat bone metastases, osteoporosis, and Paget's disease.
- They have a high affinity for hydroxyapatite crystals in bone and inhibit osteoclast activity and bone resorption.
- Nitrogen-containing bisphosphonates are more potent than early non-nitrogenous versions. Mechanisms of action differ between the two classes.
- While bisphosphonates showed
This document discusses metabolic bone diseases. It begins by describing the basic structure and function of bone, including its cellular components like osteoblasts and osteoclasts. It then discusses the constituents of bone matrix, including collagen, proteoglycans, and minerals. Bone development and homeostasis are explained, involving processes like remodeling. Specific metabolic bone diseases are then outlined in more detail, including osteogenesis imperfecta (brittle bone disease), osteomalacia/rickets due to abnormal mineralization, and hypophosphatasia due to a genetic disturbance in alkaline phosphatase synthesis. Throughout, the document provides microscopic and radiographic characteristics of these conditions.
Vitamin D plays an important role in muscle function and strength. Low vitamin D levels are associated with sarcopenia, or the loss of muscle mass and strength that occurs with aging. A study of over 800 men found that lower vitamin D levels were a significant determinant of lower relative appendicular skeletal muscle mass, even after adjusting for other factors. Another study of nearly 1,000 older adults found that lower vitamin D levels were associated with poorer performance on physical tests of mobility and strength. Maintaining adequate vitamin D levels may help reduce the risk of sarcopenia and falls in older adults.
Nutrition interventions for frailty and sarcopeniaMary Hickson
Nutritional interventions that may help combat sarcopenia and frailty include protein, essential amino acids, vitamin D, and antioxidants. While protein supplementation shows some promise, the evidence is inconsistent due to variations in study design and populations. Essential amino acid and vitamin D supplementation appear to improve muscle mass and strength, especially in deficient individuals, but more research is still needed. Overall, the evidence suggests protein and vitamin D have the most potential to treat and prevent sarcopenia, but better designed studies are required to provide definitive conclusions.
Bisphosphonates are a class of drugs that prevent bone loss and are used to treat bone metastases, osteoporosis, and Paget's disease. They have a high affinity for hydroxyapatite crystals in bone and work by inhibiting bone resorption. There are two types - non-nitrogenous bisphosphonates which induce osteoclast apoptosis, and nitrogenous bisphosphonates which inhibit protein prenylation in osteoclasts. Common indications include postmenopausal osteoporosis, glucocorticoid-induced osteoporosis, and bone metastases. While generally well-tolerated, side effects can include upset stomach, esophagus problems, and osteonecrosis of the
Muscle mass and strength decrease with age, known as sarcopenia. By age 75, sedentary adults can lose up to 30% of muscle mass. This contributes to chronic diseases and loss of physical function and independence. Resistance training and adequate protein intake can help prevent or reverse age-related muscle loss. While older adults can regain strength after training, they may have smaller gains in muscle size compared to younger adults due to diminished muscle regeneration ability with aging.
Optimizing Medical Nutrition Therapy in sarcopenia of Elderly patients Chomarhlaing
The document discusses optimizing medical nutrition therapy for sarcopenia in elderly patients. It defines sarcopenia as the loss of skeletal muscle mass and strength that occurs with aging. The prevalence of sarcopenia increases with age, affecting 5-13% of 60-70 year olds and 11-50% of those over 80. Consequences of sarcopenia include physical impairment, falls, disability and mortality. Screening tools like SARC-F can help diagnose sarcopenia based on measures of muscle mass, strength and physical performance. Management involves exercise programs and medical nutrition therapy, with a focus on adequate protein intake, particularly high-quality proteins containing amino acids like leucine, arginine and glutamine.
Presented by Linus Lay, Pharm.D. Candidate from the University of Rhode Island Class of 2022.
This presentation is on behalf of the Hackettstown Medical Center Pharmacy at Hackettstown, New Jersey as part of Continuing Education.
The Osteoporosis Overview goes over a brief introduction to osteoporosis and current/updated treatment guidelines based on global usage, drug effectiveness, and American association of clinical endocrinologists.
View MyCred Portfolio: https://mycred.com/p/2929377185
Biochemical tests are used to diagnose bone diseases. Serum tests measure calcium, phosphate, alkaline phosphatase, parathyroid hormone, and vitamin D levels. Urine tests measure calcium, phosphate, and bone turnover markers. Common bone diseases include arthritis, osteoporosis, rickets/osteomalacia, and Paget's disease. Arthritis causes joint symptoms. Osteoporosis weakens bones and increases fracture risk. Rickets/osteomalacia cause soft bones from vitamin D deficiency. Paget's disease involves abnormal bone remodeling.
Use of bisphosphonates in orthopaedic surgeryLove2jaipal
Bisphosphonates are a class of drugs used to treat bone disorders involving increased bone resorption. They work by inhibiting osteoclast activity and bone resorption. There are several generations of bisphosphonates with varying potencies, and they have many orthopedic indications including osteoporosis, bone metastases, and Paget's disease. Bisphosphonates have been shown to effectively reduce fracture risk in osteoporosis trials and decrease mortality in elderly patients at high risk for fracture. While generally well-tolerated, they can cause side effects including upset stomach and joint pain.
Cultured milk is fermented milk made using lactic acid bacteria cultures which gives it a longer shelf life of 4 days compared to 24 hours for fresh pasteurized milk. It is more digestible, providing better nutrition. Cultured milk can help those who experience stomach upset from fresh milk, and regular consumption has therapeutic properties. It can be consumed by everyone as its probiotics regulate bowel movements and maintain intestinal bacterial balance while reducing toxin production in the body.
The article is about different types of milk that can be consumed, including milk from cows, goats, sheep, and reindeer. Milk is healthy and used to make dairy products like yogurt, sour cream, and cheese. Cheese is popular because there are many varieties that differ in shape, size, and taste. Some people cannot consume dairy products or drink milk because they are allergic to it.
Vegetarianism student learning outcomes 1 unit 9helix1661
This document provides information about a lesson on Nepalese cuisine from a health and lifestyle curriculum for teens. It outlines student learning outcomes, perspectives to consider when analyzing Nepalese food including commercial, cultural, economic and environmental perspectives. It also provides stimulus questions for students to discuss Nepalese foods and includes true/false questions and activity suggestions for students related to Nepalese foods like paneer, parwal, bread, and ghee.
Energy Audit in the Dairy Industry - Sitaram Gokul Dairy Nepaleecfncci
This document summarizes an energy audit conducted at Sita Ram Gokul Milk in Kathmandu, Nepal. The audit identified opportunities to reduce waste and improve energy efficiency in areas like waste water management, energy usage, insulation, and equipment upgrades. Recommendations included installing trigger nozzles, timers, high pressure cleaners, and modifying CIP facilities to reduce water waste. Upgrades to boilers, installing variable frequency drives, and recovering heat and condensate from processes were also recommended. The company has implemented some recommendations and is working to complete other proposed upgrades.
The document outlines a business plan for NepShire, an organic dairy farm in Nepal that will breed Holstein cows, produce a variety of dairy products using modern milking pipelines, and generate bioelectricity from cow waste to help address issues in Nepal's dairy industry like the lack of product variety and reliance on expensive imported electricity. The plan discusses the company introduction, operating environment, identified opportunities, marketing strategy, feasibility analysis, and financial projections.
Cows are mainly farmed for their milk, which is taken from the farm by refrigerated tankers and brought to a factory. There, the milk is pasteurized by heating it to 71 degrees Celsius for 15 seconds to kill bacteria before being bottled or packaged for sale. Dairy cows need to have a calf each year to produce milk for human consumption. The calves are either raised as future dairy cows or for beef production.
Dairy Microbiology. Methods of preservation of milk and Milk ProductsSaugat Bhattacharjee
A vivid description of all the preservation methods of milk and milk products is present in the slides. Very useful for Microbiology, Dairy technology students.
Dairy products, especially milk, provide many essential nutrients. Milk contains protein, carbohydrates, fats, vitamins, and minerals that are important for growth, energy, bone and tooth health, and more. The document recommends daily milk consumption amounts based on age. It also discusses the processing of milk including pasteurization and fortification, different forms of milk like whole, low-fat and skim, and grades of milk quality.
This document provides an overview of milk and milk products. It discusses the composition of milk including water, fat, protein, carbohydrates, vitamins and minerals. It also covers milk flavor, contamination issues, physical properties, nutritive value, and various milk products produced through processes like fermentation, evaporation, homogenization and more. The document concludes with a discussion of common milk products like cream, butter, cheese, yogurt and ice cream.
This document summarizes the analysis of milk. It begins by defining milk and describing its typical composition, including higher fat content in buffalo milk versus cow milk. It then discusses various types of milk like standardized, whole, reduced-fat, low-fat, and skimmed milk. The document also covers milk contamination, pasteurization, long-life and UHT processed milk, evaporated and condensed milk. It provides methods to analyze milk properties like specific gravity, pH, total solids, fat content, chloride content, and titratable acidity. Finally, it discusses detecting adulterants in milk and bacteriological examination including viable bacterial count and methylene blue reduction tests.
Fermented milk products, also known as cultured dairy foods, cultured dairy products, or cultured milk products, are dairy foods that have been fermented with lactic acid bacteria.
This particular presentation describes all the fermented milk products like yoghurt, cheese etc. VIEW, SHARE, ENJOY!
Osteoporosis is a chronic disease characterized by low bone mass and deterioration of bone tissue, leading to fragile bones that are more prone to fractures. It occurs due to an imbalance between bone resorption by osteoclasts and bone formation by osteoblasts. Key factors that contribute to osteoporosis include estrogen deficiency in postmenopausal women, aging, calcium deficiency, use of corticosteroids, and lack of exercise. Preventive measures include maintaining a diet with adequate calcium and vitamin D, engaging in weight-bearing exercise, not smoking, and taking measures to prevent falls in older adults.
The document discusses biochemical markers of bone turnover. It notes that in adults, bone undergoes constant remodeling through resorption by osteoclasts and formation by osteoblasts. Biochemical markers measure bone formation or resorption products in blood and urine, allowing serial assessment of bone turnover. Formation markers include osteocalcin and procollagen peptides, while resorption markers include collagen telopeptides and hydroxypyridinium cross-links. These markers can help evaluate treatment response, predict fracture risk and bone loss, and select patients who may benefit most from treatment. However, markers have limitations due to biological and analytical variability.
This document discusses osteoporosis and bone fragility. It begins by defining key terms like osteoporosis, bone fragility, and T-scores. It then discusses the importance of both bone quantity and quality in determining fracture risk. The document outlines the key regulators of bone remodeling like RANK, RANKL, and OPG. It explains how chronic immune activation can uncouple the bone remodeling process and lead to increased fragility through a diversion of stem cell differentiation toward osteoclast formation. Finally, it discusses how biomarkers can help evaluate nutritional interventions aimed at reducing inflammation and supporting bone health.
Previous year question on osteoporosis based on neet pg, usmle, plab and fmge...Abhishek Gupta
Dual energy X-ray absorptiometry (DEXA) is considered the gold standard for diagnosing osteoporosis. It is a quantitative method for measuring bone mass using low energy X-rays. The World Health Organization criteria for osteoporosis is a DEXA T-score at or below -2.5. Ultrasound, single energy X-ray absorptiometry, and quantitative computed tomography are not as accurate as DEXA for diagnosing osteoporosis.
Osteoporosis is a disease characterized by reduced bone mass and deterioration of bone tissue, leading to an increased risk of bone fractures. It is defined as a bone mineral density (BMD) score of more than 2.5 standard deviations below the average for a young healthy adult. Osteoporosis affects many post-menopausal women and older adults due to age-related bone loss. It has no symptoms until a fracture occurs, with vertebral compression fractures and wrist fractures being common. Diagnosis involves assessing risk factors and performing BMD tests and imaging to evaluate for fractures.
Strontium Renelate and OsteoPorosis By Mohammed Zamir Mirza.pptxMOHAMMED ZAMIR MIRZA
Strontium ranelate is a treatment for osteoporosis that works by increasing bone formation and decreasing bone resorption, similarly to choline-stabilized orthosilicic acid. It is 25% bioavailable and has a half-life of 60 hours. Studies show it increases bone mineral density and reduces fracture risk. Common side effects include diarrhea and nausea. The recommended dosage is 2 grams taken before bed with water.
This document discusses osteoporosis and bone health. It begins by noting the impact of osteoporosis on older patients, including increased hospital admissions and length of stay. It then discusses definitions of osteoporosis from WHO and treatment gaps. The document covers bone structure, cells, mineralization, remodeling cycles, and factors influencing bone health like hormones and lifestyle. Diagnostic methods like DXA are summarized. Treatment options focused on prevention of fractures through calcium, vitamin D, bisphosphonates, PTH, and fall prevention are outlined.
This document discusses how a diet containing adequate amounts of high-quality protein, especially from dairy sources, can help protect bone health and reduce the risk of osteoporosis during aging. It outlines that bone is constantly remodelling and needs nutrients like calcium, protein, and vitamins D and K to maintain strength. While high-protein diets were thought to negatively impact bones by increasing calcium loss, studies now show that protein also increases calcium absorption, helping balance calcium levels. Dairy products provide both protein and calcium to support bone and muscle health during aging.
Osteoporosis is a disease characterized by low bone mass and deterioration of bone structure. It increases the risk of fractures. The World Health Organization defines osteoporosis as a bone density 2.5 standard deviations or more below the mean bone density of healthy young adults. Dual-energy x-ray absorptiometry (DXA) is the gold standard test used to diagnose osteoporosis by measuring bone mineral density at sites like the hip and spine. Lifestyle factors like diet, exercise, smoking and alcohol as well as certain medical conditions and medications can impact bone health and increase the risk of osteoporosis.
Paget’s disease of bone with special reference to dentistry-an insightishita1994
This document provides an overview of Paget's disease of bone, covering its introduction, epidemiology, pathogenesis, clinical features, diagnosis, and treatment. Paget's disease is characterized by excessive and abnormal bone remodeling, resulting in weakened and deformed bones. It is caused by genetic and environmental factors and involves abnormal osteoclast activity and increased bone formation. Clinically, it can cause bone pain, deformity, and fractures. Diagnosis involves radiographic imaging showing abnormal bone patterns and histopathological examination of bone samples. Treatment focuses on reducing bone turnover through medications like bisphosphonates.
The document summarizes the mechanism of alveolar bone destruction in periodontitis. It discusses the structure of alveolar bone and the process of bone remodeling which is regulated by factors that control bone resorption and formation. Key cytokines like IL-1, IL-6, TNF-α play a role in bone resorption by stimulating osteoclastogenesis directly or indirectly via prostaglandins. The balance between these resorptive and formative factors is important in maintaining bone homeostasis, and an imbalance leads to periodontal bone loss.
This document discusses the importance of fetal movement for proper skeletal development. Reduced or absent fetal movement can lead to joint contractures, thin and brittle bones, and overall growth issues in infants. This condition is known as fetal akinesia deformation sequence (FADS). Animal models and genetic studies have provided evidence that mechanical stimulation from fetal movement is crucial for coordinating cartilage and bone development through various cell signaling pathways. A better understanding of how movement impacts skeletogenesis could help develop preventative and therapeutic approaches for skeletal disorders.
This document discusses osteoporosis and bone health. It provides statistics on osteoporosis prevalence and consequences. It identifies key risk factors for osteoporosis like low calcium intake, lack of physical activity, smoking, alcohol, gender, and small body size. It explains how estrogen helps maintain bone density and how bone loss increases after menopause. Recommended daily calcium intake levels are provided for different age groups. The benefits of an Ossein mineral complex supplement called OSS-PRO are described, including its ability to prevent and heal fractures by providing proteins and minerals that stimulate bone growth.
Dose–Response Relationships Between Energy Availability and Bo.docxmadlynplamondon
Dose–Response Relationships Between Energy Availability and Bone
Turnover in Young Exercising Women*
Rayan Ihle and Anne B Loucks
ABSTRACT: To help refine nutritional guidelines for military servicewomen, we assessed bone turnover after
manipulating the energy availability of 29 young women. Bone formation was impaired by less severe
restrictions than that which increased bone resorption. Military servicewomen and others may need to
improve their nutrition to avoid these effects.
Introduction: We determined the dose–response relationship between energy availability (defined as dietary energy
intake minus exercise energy expenditure) and selected markers of bone turnover in 29 regularly menstruating,
habitually sedentary, young women of normal body composition.
Materials and Methods: For 5 days in the early follicular phase of two menstrual cycles separated by at least 2
months, subjects expended 15 kcal/kgLBM/day in supervised exercise at 70% of aerobic capacity and consumed
controlled amounts of a clinical dietary product in balanced (45 kcal/kgLBM/day) and one of three restricted (either
10, 20, or 30 kcal/kgLBM/day) energy availability treatments in random order. Blood was sampled at 10-minute
intervals, and urine was collected for 24 h. Samples were assayed for plasma osteocalcin (OC), serum type I
procollagen carboxy-terminal propeptide (PICP), and urinary N-telopeptide (NTX).
Results: NTX concentrations (p � 0.01) and indices of bone resorption/formation uncoupling (ZNTX-OC and ZNTX-PICP;
both p � 10�4) were increased by the 10 kcal/kgLBM/day treatment. OC and PICP concentrations were suppressed by
all restricted energy availability treatments (all p � 0.05). PICP declined linearly (p � 10�6) with energy availability,
whereas most of the suppression of OC occurred abruptly between 20 and 30 kcal/kgLBM/day (p � 0.05).
Conclusions: These dose–response relationships closely resembled those of particular reproductive and metabolic
hormones found in the same experiment and reported previously: similar relationships were observed for NTX and
estradiol; for PICP and insulin; and for OC, triiodothyronine (T3), and insulin-like growth factor (IGF)-I. The uncoupling
of bone resorption and formation by severely restricted energy availability, if left to continue, may lead to irreversible
reductions in BMD, and the suppression of bone formation by less severe restrictions may prevent young women from
achieving their genetic potential for peak bone mass. More prolonged experiments are needed to determine the dose–
response relationships between chronic restrictions of energy availability and bone turnover.
J Bone Miner Res 2004;19:1231–1240. Published online on April 19, 2004; doi: 10.1359/JBMR.040410
Key words: bone markers, energy availability, exercise, bone formation, bone resorption
INTRODUCTION
THE U.S. DEPARTMENT of Defense has an immediate needto reduce the prevalence of stress fractures in military
servicewomen. Over a period of 20 ye ...
Osteoporosis is a chronic, progressive metabolic bone disease characterized by porous bone and structural deterioration of bone tissue, leading to increased bone fragility and fracture risk. It is caused by an imbalance between bone resorption and formation where resorption exceeds formation. Risk factors include female gender, older age, small body frame, family history, smoking, excessive alcohol, low calcium intake, and medical conditions like hyperthyroidism. Diagnosis is made through bone mineral density tests and x-rays. Treatment focuses on lifestyle changes, calcium and vitamin D supplementation, as well as medications to reduce resorption and increase formation.
Osteoporosis is a bone disorder characterized by low bone density and mass, leading to an increased risk of fractures. It is a growing epidemic, with over 75 million cases in the US, Europe and Japan expected to increase further. Risk factors include age, gender, family history, lifestyle factors like smoking, sedentary lifestyle, and certain medical conditions or medications. Diagnosis involves clinical evaluation, bone density scans, and biochemical markers. Treatment focuses on lifestyle changes like exercise, calcium intake, and vitamin D; medications include hormones, biphosphonates, and teriparatide injections in severe cases. Preventing osteoporosis requires modifiable lifestyle changes and responsible self-care.
In this webinar on bone health Rousselot explains the role of osteopenia, the pre-stage to osteoporosis, how it can affect our lives and how to prevent it. Dr. Elke de Clerck presents the science behind and importance of Peptan collagen peptides, a pure protein, with specific benefits to support stronger and healthier bones.
Rousselot is an official Nutrition Supporter of World Osteoporosis Day in 2015.
Watch webinar on https://www.youtube.com/watch?v=daRY5gXd6AQ
Presenter:
Dr. Elke de Clerck, Technical Support and Development Manager at Rousselot, Elke holds a PhD degree in Biotechnology from Ghent Unviersity and has over 10 years of international experience. She is based in Ghent, Belgium, where Rousselot’s expertise center is located.
About Rousselot
Rousselot® is the leading manufacturer of gelatine and collagen peptides to the food, pharmaceutical and nutraceutical industries. Rousselot manufactures Peptan, a globally recognized brand, offering a wide range of collagen peptides scientifically proven to improve overall joint health, mobility, bone structure and the natural beauty of skin.
http://www.peptan.com
The starting template material is RNA not DNA ( as in PCR assays for the diagnosis of viral infections)
RNA cannot serve as a template for PCR, (RNA is not a substrate for the Taq DNA polymerases commonly utilised in PCR.) Therefore reverse transcription is combined with PCR to convert RNA into a complementary DNA (cDNA)) suitable for PCR
The first step in this procedure is to convert the RNA molecules into single-stranded complementary DNA (cDNA) (Figure 9.20). Once this preliminary step has been carried out, the PCR primers and Taq polymerase are added and the experiment proceeds exactly as in the standard technique
Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
10 Benefits an EPCR Software should Bring to EMS Organizations Traumasoft LLC
The benefits of an ePCR solution should extend to the whole EMS organization, not just certain groups of people or certain departments. It should provide more than just a form for entering and a database for storing information. It should also include a workflow of how information is communicated, used and stored across the entire organization.
These lecture slides, by Dr Sidra Arshad, offer a simplified look into the mechanisms involved in the regulation of respiration:
Learning objectives:
1. Describe the organisation of respiratory center
2. Describe the nervous control of inspiration and respiratory rhythm
3. Describe the functions of the dorsal and respiratory groups of neurons
4. Describe the influences of the Pneumotaxic and Apneustic centers
5. Explain the role of Hering-Breur inflation reflex in regulation of inspiration
6. Explain the role of central chemoreceptors in regulation of respiration
7. Explain the role of peripheral chemoreceptors in regulation of respiration
8. Explain the regulation of respiration during exercise
9. Integrate the respiratory regulatory mechanisms
10. Describe the Cheyne-Stokes breathing
Study Resources:
1. Chapter 42, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 36, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 13, Human Physiology by Lauralee Sherwood, 9th edition
Histololgy of Female Reproductive System.pptxAyeshaZaid1
Dive into an in-depth exploration of the histological structure of female reproductive system with this comprehensive lecture. Presented by Dr. Ayesha Irfan, Assistant Professor of Anatomy, this presentation covers the Gross anatomy and functional histology of the female reproductive organs. Ideal for students, educators, and anyone interested in medical science, this lecture provides clear explanations, detailed diagrams, and valuable insights into female reproductive system. Enhance your knowledge and understanding of this essential aspect of human biology.
- Video recording of this lecture in English language: https://youtu.be/Pt1nA32sdHQ
- Video recording of this lecture in Arabic language: https://youtu.be/uFdc9F0rlP0
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptxHolistified Wellness
We’re talking about Vedic Meditation, a form of meditation that has been around for at least 5,000 years. Back then, the people who lived in the Indus Valley, now known as India and Pakistan, practised meditation as a fundamental part of daily life. This knowledge that has given us yoga and Ayurveda, was known as Veda, hence the name Vedic. And though there are some written records, the practice has been passed down verbally from generation to generation.
Osteoporosis - Definition , Evaluation and Management .pdfJim Jacob Roy
Osteoporosis is an increasing cause of morbidity among the elderly.
In this document , a brief outline of osteoporosis is given , including the risk factors of osteoporosis fractures , the indications for testing bone mineral density and the management of osteoporosis
Osteoporosis - Definition , Evaluation and Management .pdf
Odenxrelfclinicaltrial
1. Osteoporos Int
DOI 10.1007/s00198-009-0839-8
ORIGINAL ARTICLE
Milk ribonuclease-enriched lactoferrin induces positive
effects on bone turnover markers in postmenopausal women
S. Bharadwaj & A. G. T. Naidu & G. V. Betageri &
N. V. Prasadarao & A. S. Naidu
Received: 17 October 2008 / Accepted: 12 December 2008
# International Osteoporosis Foundation and National Osteoporosis Foundation 2009
Abstract aged 45 to 60 years were randomized into placebo or
Summary Current treatments for postmenopausal osteopo- RNAse-enriched-LF (R-ELF) supplement groups. The bone
rosis suffer from side effects. Safe and natural milk health status was monitored by assessing bone resorption
proteins, ribonuclease, and lactoferrin promote formation markers, serum N-telopeptides (NTx), and urine deoxypyr-
of new capillaries and bone formation. A ribonuclease- idinoline (Dpd) crosslinks and serum bone formation
enriched lactoferrin supplement studied here, demonstrates markers, bone-specific alkaline phosphatase (BAP), and
significant reduction in resorption and increase in formation, osteocalcin (OC).
towards restoring the balance of bone turnover within Results R-ELF supplementation demonstrated a decrease in
6 months. urine Dpd levels by 14% (19% increase for placebo) and
Introduction Osteoporosis, a major health issue among serum NTx maintained at 24% of the baseline (41% for
postmenopausal women, causes increased bone resorption placebo), while serum BAP and OC levels showed a 45%
and reduced bone formation. A reduction in angiogenesis and 16% elevation (25% and 5% for placebo).
could also contribute to this imbalance. Current treatments Conclusions R-ELF supplementation demonstrated a sta-
such as hormone replacement therapy and bisphosphonates tistically significant reduction in bone resorption and
have drawbacks of severe side effects. Milk ribonuclease increase in osteoblastic bone formation, to restore the
(RNase) is known to promote angiogenesis and lactoferrin balance of bone turnover within a short period.
(LF) to stimulate bone formation by osteoblasts. We
examine the effect of ribonuclease-enriched lactoferrin Keywords Lactoferrin . Osteoporosis . Postmenopause .
supplement on the bone health of postmenopausal women. Ribonuclease
Methods A total of 38 healthy, postmenopausal women,
S. Bharadwaj : A. G. T. Naidu : A. S. Naidu (*) Introduction
N-terminus Research Laboratory,
981 Corporate Center Dr., # 110, Osteoporosis is a bone and joint disorder that causes a
Pomona, CA 91768, USA significant reduction in bone density and alteration of the
e-mail: asnaidu@nterminus.com
bone microstructure that primarily affects elderly women.
G. V. Betageri These chronic changes in the interior of bone tissue lead to
Department of Pharmaceutical Sciences, College of Pharmacy, fractures that could have adverse influence on the quality of
Western University of Health Sciences, life of the elderly. The US National Osteoporosis Foundation
309 E Second Street,
Pomona, CA 91766, USA has estimated that by 2010, about 12 million people over
the age of 50 are expected to have osteoporosis and
N. V. Prasadarao another 40 million to have low bone mass (osteopenia). In
Division of Infectious Diseases, Childrens Hospital Los Angeles addition, osteoporosis also affects one in eight men
and Keck School of Medicine, University of Southern California,
4650 Sunset Blvd., worldwide [1, 2]. Bones undergo a continuous remodeling
Los Angeles, CA 90027, USA process through repeated cycles of destruction and
2. Osteoporos Int
rebuilding. In healthy young adults, the amount of new appropriate age-matched control that received only calcium
bone formation approximately balances the amount of supplement. The bone health status was assessed by well-
bone resorption. As the age increases, however, the established assays for markers of bone resorption and bone
balance shifts to favor bone resorption. Among the formation. Our studies have, for the first time, demonstrated
numerous factors that contribute to the development of that R-ELF significantly reduced the bone resorption
osteoporosis in women, postmenopausal estrogen defi- markers and simultaneously increased the bone formation
ciency accelerates bone loss of 1–5% per year during the markers; and suggest possible utilization of R-ELF in
first decade after menopause. Current efforts to treat bone natural supplements for osteoporosis without significant
diseases have primarily concentrated on the development side effects.
of drugs to block bone resorption, which decrease the
formation or activity of osteoclasts. Present treatment
options for postmenopausal osteoporosis include hormone Materials and methods
replacement therapy (HRT) and bisphosphonates. HRT is
known to significantly reduce osteoclast activity but is Subjects
prone to adverse effects, such as increased risk of breast
cancer [3, 4], and bisphosphonates have a risk of More than 50 women responded to the announcement about
development of esophageal ulcers [5]. Therefore, it is this study made through notification in a local community
imperative to explore and develop strategies for enhancing organization. All of the prospects completed a question-
the bone formation and simultaneously prevent the bone naire on general bone health status, previous injury/disease,
loss without side effects. current or previous treatment, and consumption of calcium-
Milk, a superior source of bioavailable calcium, has rich foods. General health was determined by routine
pronounced effects on bone metabolism. The basic protein standard medical assessment of physical and mental health.
fraction of milk contains several active components that The exclusion criterion for the study included potential risk
have been shown to suppress osteoclast-mediated bone factors for osteoporosis, dietary calcium intake, and
resorption and osteoblast differentiation. Studies on milk medical history. Women who had history of any illness
basic protein (MBP) intake have demonstrated bone- (active Paget’s disease, hyperthyroidism, hypothyroidism,
strengthening effects in cell culture studies and animal type I diabetes mellitus, calcium intolerance, kidney
experiments [6]. A limited number of studies report the problems; cancer diagnosis for solid malignancies, and
influence of MBP supplementation on bone metabolism inflammatory bowel disease) that affect bone mineral
and radial bone mineral density in healthy adult women [7, metabolism were excluded. Women that received treatment
8]. Recently, the component of MBP responsible for the with estrogens, progesterone, raloxifene, or tamoxifen and
inhibition of osteoclastic resorption has been shown to be antiresorptive agents like calcitonin or bisphosphonates
identical to milk angiogenin, a 14-kDa milk basic protein were also excluded. We also excluded women with life
that exhibits both angiogenic and RNAse properties [9]. expectancy of less than 2 years; current and ongoing use of
Angiogenesis or formation of new capillaries within bone methotrexate, phenytoin, phenobarbital, or inhaled cortico-
tissue could facilitate supply of nutrients and removal of steroids at a dose greater than 800 μg/day; and a body mass
waste products and may be responsible for healing of index above 32 or below 20. On evaluation, 38 healthy,
fractures, remodeling and regeneration [10, 11]. ambulatory postmenopausal women, 45–60 years old, with
Lactoferrin (LF), a multi-functional protein, present in no menses for at least 12 months were registered for the
neutrophils and exocrine secretions like milk and tears, is study. Every effort was made to recruit only those women
also present in synovial fluid of bone joints. LF is a major who fulfilled the inclusion and exclusion criteria. Nonethe-
constituent of colostrum responsible for the rapid growth less, there were three exclusions, one with a history of
and development of skeletal and immune system of the treatment for bone health and other two with hypothyroid-
newborn. Recent studies have established LF as a bone ism. The study was approved by the appropriate Institu-
growth factor as it stimulates osteoblast differentiation and tional Review Board of the Western University of Health
new bone formation; and reduces bone resorption in vitro Sciences in Pomona, CA, USA. Prospective participants
and in animal models [12, 13]. LF is also a transport protein were advised of the nature of the study and provided
that could facilitate absorption of many essential minerals written informed consent before participation.
and nutrients that bind to it; however, the effect of LF on
bone health in humans is not known. The objective of the Study design
present study is to investigate the benefits of milk RNAse-
enriched LF (R-ELF) supplement along with calcium on Thirty-five women included into the study were randomly
bone health of postmenopausal women in comparison to an assigned to one of the two groups: placebo group or R-ELF
3. Osteoporos Int
group. R-ELF is a ribonuclease (angiogenin)-enriched lacto- levels of bone-specific alkaline phosphatase in the serum
ferrin either co-isolated from bovine milk (50:50 ratio wt/wt) (sBAP) [16] and (2) change in serum levels of intact bone gla
or both proteins admixed to obtain required ratios, as protein or osteocalcin (sOC) [17]. Bone resorption was also
previously described [14, 15]. There were 15 subjects in investigated by identifying the change in levels of two
the placebo group and were supplemented with 100% resorption markers, N-telopeptides in the serum (sNTx) [18]
recommended daily allowance (RDA) of calcium, in tablet and free deoxypyridinoline crosslinks in urine (uDPD) [19].
form, whereas 20 subjects of the R-ELF group were These four bone turnover markers were monitored in the
administered with two R-ELF capsules of 125 mg each, urine and blood samples collected from each subject, before
along with 100% RDA of calcium administered orally from R-ELF supplementation (baseline) and with R-ELF supple-
day 1 to day 180. Venous blood (by standard venipuncture mentation at the end of 15, 30, 60, 90, and 180 days. Metra-
technique) and urine samples were collected from each BAP, Metra-OC, and Metra-DPD antibody immunoassay
subject on day 0 (baseline before the commencement of kits used for the study were obtained from Quidel, San
supplementation), day 15, day 30, day 60, day 90, and Diego, CA, USA. Osteomark NTx enzyme immunoassay
day 180 of the study. Standard systolic/diastolic blood kit was purchased from Inverness, Princeton, NJ, USA.
pressures as well as the body weight were also monitored at Urinary creatinine was determined using standard colori-
baseline and the aforementioned days. All the participants metric assay (Oxford Biomedical Research, Oxford, MI,
were interviewed at each visit for adherence to the regimen USA) based on well-known Jaffe reaction [20].
and occurrence of adverse events. A flow diagram of the
study is shown in Fig. 1. Statistical analysis
Biochemical markers of bone turnover Biochemical bone turnover marker data for each observa-
tional day was analyzed for measures of central tendency,
Venous blood was drawn into a vacutainer (BD Bioscien- deviation, and distribution of data. Data were considered
ces, NJ, USA) by standard venipuncture technique. The outliers, if they were >1.5 times the inter-quartile range
blood was allowed to clot and the serum was separated by above the third quartile or below the first quartile. Outliers
centrifugation. The serum specimens were stored at −80°C were discarded from datasets for statistical tests of
until analysis. Urine was collected after an overnight fast significance. In view of the small size of placebo and R-
and frozen at −20°C until analysis. On the day of analysis, ELF groups, median and standard error of the mean were
serum and urine samples were thawed, mixed, centrifuged, used as the preferred measures of central tendency
and the clear supernatant was used for the assay. Bone throughout this study, as it is least influenced by the
formation rates were assessed by measuring two well- extremes of data. The Kolmogorov–Smirnov test (KS test)
established markers of osteoblast activity: (1) change in was used for normal distribution of data within each set
[21]. Non-linear least-squares regression of the marker data
to a logistics curve was performed to evaluate the peak
Registration
levels of bone turnover markers at the end of the study.
(n = 38)
Student’s unpaired two-sample t test was used for compar-
ison of the mean observed change in markers for placebo
EXCLUSIONS
Past treatment for bone health (n = 1)
and R-ELF datasets in order to establish the effect of R-
Hypothyroidism (n = 2) ELF supplementation. OriginPro Ver. 8 (OriginLab, MA,
USA) software was used for data analysis.
Randomization
(n = 35)
Results
CONTROL Group R-ELF Group
(n = 15) (n = 20) Baseline characteristics, compliance, and adverse events
Adverse Events (n = 0) Adverse Events (n = 0)
The baseline characteristics of placebo and R-ELF groups
Withdrawal (n = 3) Non-compliance (n = 1) are shown in Table 1. The data shows a comparable match
between the placebo and R-ELF groups, i.e. generally good
bone health status and distribution of the bone turnover
Analyses Analyses
Completed (n = 12) Completed (n = 19)
marker levels. The median and range of markers are within
the accepted levels for generally healthy, postmenopausal
Fig. 1 Flow-chart of the study women [22–32]. Three participants from the control group
4. Osteoporos Int
Table 1 Baseline characteris-
tics of the study population Characteristic Typical values for Control R-ELF
PM womena
Number of participants (n) 15 20
Age (years)
Mean±SD 51.0±4.4 53.5±5.4
Range 45–59 45–60
Weight (lbs)
Mean±SD 134±20 141±24
Range 104–174 107–208
Blood pressure (mm Hg)
Mean systolic 121 127
Mean diastolic 78 80
Bone resorption status
a
Reference [20–30] Serum NTx (nM BCEb) 15.9 (8–28) 15.8±2.6c (5.3–29.1) 12.9±3.3 (7.8–41.6)
b
Bone collagen equivalents Urine Dpd (nM/mM CRd) 7.5 (4–12) 6.6±0.7 (5.2–11.7) 8.2±0.6 (6.0–13.2)
c
Median±SEM given for all Bone formation status
markers. Range shown in Serum BAP (U/L) 25 (14–43) 25.0±1.3 (18.9–30.6) 19.7±2.4 (13.1–44.8)
parenthesis Serum OC (ng/mL) −3–10 4.1±0.5 (2.1–7.0) 4.2±0.4 (2.6–9.8)
d
Creatinine
dropped out of the study before day 15 and one from the Bone resorption markers
R-ELF group was dropped out from the study due to non-
compliance. There was >95% compliance to the supple- The median sNTx and uDpd changed gradually to a peak
ment regimen among the subjects. The body weight and level for both placebo as well as R-ELF groups, as shown
blood pressures of all the subjects essentially maintained in Fig. 2. The resorption markers for each observational day
within ±3% of their baseline values. No adverse events were also normally distributed (p=0.34–0.99). sNTx for the
were reported during the 6-month study or 3-month post- placebo group increased from 15.8±2.6 nM bone collagen
study follow-up. equivalents (BCE) on day 0 to 22.1±1.7 nM BCE on
Fig. 2 Variation of bone resorp-
tion markers—sNTx (a) and
uDpd (b) and bone formation
markers—sBAP (c) and sOC (d)
with the progress of the study.
Median±SEM data are shown
for placebo (unfilled square) and
R-ELF (filled square) groups
5. Osteoporos Int
Fig. 3 Change from the base-
line of median bone turnover
markers with the progress of the
study—sNTx (a), uDpd (b),
sBAP (c), and sOC (d). Open
bars denote the placebo group
and filled bars denote R-ELF
group in all the panels. In the
case of sOC, change in mean
from baseline level is shown
day 180, while R-ELF group displayed a relatively smaller placebo group, indicating that R-ELF supplementation
rise (12.9±3.3 to 16.1±2.0 nM BCE). The change in bone induces its effects within a short time. The calculated
turnover markers, calculated as a percent of the parameters for the bone markers and the results of statistical
corresponding baseline levels are represented in Fig. 3. tests are summarized in Table 2.
Median sNTx for the placebo group showed an increase of An interesting reversal of trend was observed with
40.1% in 180 days, reflecting significant bone resorption median uDpd levels although the placebo group showed an
while the R-ELF group showed a relatively smaller rise of increase from 6.6±0.8 to 7.7±0.7 by day 180, the R-ELF
24.5% during the same period (p<0.001, 95% CI). The group decreased from 8.2±0.6 to 6.9±0.6 nM Dpd/mM
duration to achieve 80% of the peak change in sNTx is Creatinine. The overall rise of 17.8% indicated a significant
about 25 days for R-ELF group compared to 45 days for the level of bone resorption in the placebo group. In contrast,
Table 2 Progress of biochem-
ical bone turnover markers and Marker Change from baseline (%) Time to reach 80% of peak t testc
statistical analysis level in days
Mediana Peakb
Bone resorption markers
Serum NTx
Placebo 32.0±7.6 41.6 45 15.18
R-ELF Group 20.2±4.0 24.1 25 <0.001
Urine Dpd
Placebo 5.6±3.3 19.2 95 4.11
a
Median±SEM R-ELF Group −10.7±2.2 −14.0 31 <0.01
b
Peak change in the marker Bone formation markers
obtained from a non-linear least
Serum BAP
squares fit to logistics curve
c
Value of the t statistic. Signif- Placebo 9.1±3.9 25.4 115 4.10
icance p (95% CI) is given in R-ELF Group 33.2±7.2 44.9 45 <<0.001
parenthesis Serum OC
d
Not determined as there was Placebo 0.4±1.0 5.1 –d −20.3
no significant change in serum R-ELF Group 7.2±2.8 16.4 – <0.001
OC for the control group
6. Osteoporos Int
Dpd levels of the R-ELF group showed a reduction in resorp- those for the R-ELF group increased linearly by 18.8% from
tion by ∼10% within 30 days and continued to fall to 14.6% 4.3±0.4 to 5.2±0.5 ng/mL. The results summarized in Table 2
by the end of the study (p=0.0021, 95% CI). The R-ELF indicate that change in sOC with supplementation was
group achieved 80% of peak change in Dpd levels in about statistically significant (p<0.001, 95% CI).
31 days, compared to 95 days taken by the placebo group. Bone formation markers were observed to be highly
correlated with bone resorption markers for both groups,
Bone formation markers with Pearson correlation coefficient (r) values in the range
0.58–0.93 for the placebo and 0.66–0.90 for the R-ELF
The two markers of bone formation, sBAP and sOC, were group, respectively. The correlation plots along with the
determined at the same pre-defined intervals during the study. statistical parameters are shown in Fig. 4. The positive
Figure 2 shows the measured variation of median sBAP and correlation observed for placebo group is generally improved
sOC levels for both groups. The range of observed sBAP and with R-ELF supplementation, as seen from the higher r and
sOC values are similar to that reported in other recent studies smaller p values for sNTx with sBAP as well as sOC. In
[22–32]. As with the bone resorption markers, the sBAP and case of uDpd, the positive correlation seen with the placebo
sOC datasets for each observational day were normally group is changed to negative for the R-ELF group—r
distributed (p=0.39–0.98). changing from 0.93 to −0.87 for sBAP and from 0.83 to
The variation of sBAP and sOC from their respective −0.66 for sOC, respectively. This change reflects the effect
baseline levels is depicted in Fig. 3. Median sBAP of R-ELF supplementation to reduce resorption markers
gradually increased to a peak level for both the groups while increasing the formation markers to restore balance of
(25.0±1.3 to 31.4±3.0 U/L for placebo and 19.7±2.4 to bone turnover.
28.1±3.1 U/L for the R-ELF group). Although median
levels for R-ELF group are lower than those for the placebo
group, the percentage change from baseline was better for Discussion
the R-ELF group. The 42.7% elevation for R-ELF group
compared to 25.7% for the placebo was also statistically Clinical studies of large populations of postmenopausal
significant (p<0.001, 95% CI). The peak level attained was women have established that biochemical markers of bone
about twice that of the placebo group and 80% of peak change metabolism such as serum osteocalcin, bone-specific alkaline
was achieved within ∼45 days of R-ELF supplementation. In phosphatase, and the urinary excretion of cross-linked
the case of sOC, mean marker levels maintained within ±3% collagen N-telopeptides are indicators of loss of bone
of baseline for placebo (4.1±0.5 to 4.2±0.4 ng/mL), while mineral density, which in turn is a risk for osteoporosis and
Fig. 4 Correlation plots of bone formation markers vs. bone resorption markers. Top row corresponds to the placebo group and the bottom row to
the R-ELF group. The Pearson correlation coefficient (r) and significance (p) are shown for each plot
7. Osteoporos Int
fractures. In the present study, R-ELF supplementation has isosorbide mononitrate (ISMO) showed a 45% decrease in
been shown to improve bone formation markers, while resorption markers and a 23% increase in formation
reducing the bone resorption in postmenopausal women. In markers compared to the placebo group [40]. However,
addition, R-ELF supplementation is able to achieve this ISMO induced mild to moderately severe headaches in
significant change in bone turnover markers within a short some participants in that study. In cardiovascular health
duration. The ability of R-ELF supplementation to improve studies, nitrates have been known to cause this side effect in
bone metabolism is attributed to the characteristics of its key as many as 36–52% of participants [42]. In a recent clinical
components, RNAse and LF. Firstly, LF is a transport study of PTH [32, 41], there was a 92% enhancement of
protein and present in all exocrine secretions in the body sBAP, but was accompanied by 72% increase in bone
including synovial fluid in the joints. Specific LF receptors resorption as measured by uDpd. Although teriparatide has
have been described in mammalian cell types and tissues been approved, PTH treatment is known to have adverse
including monocytes, lymphocytes, platelets, liver, mamma- effects, at least in animal model studies [43, 44] and
ry epithelial cells, and intestine [33]. LF also interacts with requires further long-term evaluation [41]. Of note, similar
low-density lipoprotein receptor-related protein 1 in osteo- elevation of bone formation marker was observed by daily
blasts and increases the mitogenic activity, indicating that LF oral supplementation of R-ELF in the present study,
enhances the bone growth. [34]. It can also form complexes compared to subcutaneous injection of PTH. Therefore, R-
with many nutrients like the glucosaminoglycans, due to its ELF supplementation would provide alternative treatment
highly positive charge. Therefore, LF is able to interact with without significant adverse effects.
cells and may deliver the nutrients to key locations in bones Correlations between bone turnover markers for some
and joints. Furthermore, LF is also known to stimulate studies of interventions with HRT, prednisone and teripara-
osteoblastic activity [12, 13]. Secondly, formation of new tide [26, 28, 32] were compared with our results. Similar to
capillaries and supply of nutrients is essential for the the present study, a generally improved correlation between
rejuvenation of the aging bone tissue. Milk RNAse present resorption and formation markers with the intervention was
in the R-ELF may accomplish this function, as it is known to observed. However, the correlation did not change from
stimulate angiogenesis [35]. positive (for placebo) to negative for the treatment group.
Several strategies for the restoration of postmenopausal This is so because reduction in resorption by HRT and
bone turnover have been developed and established with bisphosphonate treatments is accompanied by significant
the support of bone mineral density data over the last decrease in bone formation marker like BAP [45].
decade, and have been approved for therapy. Bisphospho- Although teriparatide treatment resulted in favorable in-
nates, like alendronate and its variants, have been used for crease in BAP, it was associated with increased resorption
treatment of age-related bone loss in postmenopausal levels [41]. In both these cases, the correlation between the
women and have consistently shown substantial reduction formation and resorption markers remained positively
in bone resorption. However, this reduction in resorption is correlated even after intervention, leading away from a
also accompanied by up to 40% decrease in bone formation balance of bone turnover. A negative correlation between
as reflected by sBAP and sOC markers in general, and as the markers is a condition of increased bone formation and
high as 52% reduction in one trial [29, 30, 36]. In HRT or reduced resorption leading to attainment of the balanced
estrogen therapy trials, a reduction by 30–50% of resorp- bone turnover and is the preferred state of outcome. In the
tion has been observed along with 20–45% reduction in present study, uDpd is negatively correlated with formation
bone formation makers [26, 36]. Selective estrogen receptor markers, sBAP and sOC, after R-ELF supplementation; and
modulator such as raloxifene hydrochloride has shown a therefore, appears to lead towards restoring the balance.
gradual 25–30% decrease of resorption markers in 3 years In summary, R-ELF supplementation in preliminary
along with 10–20% decrease in formation markers [37, 38]. human clinical trials, for the first time, has shown
In contrast to above treatment options, R-ELF not only promising and favorable effect on biomarkers of bone
reduced the resorption markers by about 20% but also turnover in postmenopausal women. Despite the small
affected bone formation rate positively (up to 40% number of subjects, short duration and lack of bone density
increase), within 3 months of supplementation. data in the present study; and in view of the several
Strontium renelate, isosorbide mononitrate, and teripara- shortcomings of drug therapy for postmenopausal bone
tide (synthetic parathyroid hormone (PTH)) are among the loss, the results of R-ELF supplementation are very
few other therapeutic agents that show a positive effect on significant, as it is based on safe and natural milk proteins.
bone formation as well as a reduction in bone resorption
activity [39–41, 32]. Organic nitrates stimulate osteoclasts
and osteoblasts via the production of NO and have been Acknowledgements We thank Tiffani Davis (phlebotomist), Natver
observed to elevate bone formation levels. In a recent study, Patel, and Sreus Naidu for coordinating with the clinical study.
8. Osteoporos Int
Funding This project was funded by N-terminus Research Labora- 21. Zar JH (1999) Biostatistical analysis, 4th edn. Prentice Hall, NJ, p 475
tories, Pomona, CA, USA. 22. Eastell R, Mallinak N, Weiss S et al (2000) Biological variability
of serum and urinary N-telopeptides of type I collagen in
postmenopausal women. J Bone Miner Res 15:594–598
23. Scariano JK, Glew RH, Bou-Serhal CE et al (1998) Serum levels
Conflicts of interest S. Bharadwaj, A. G. Tezus Naidu, and A. S. of cross-linked N-telopeptides and aminoterminal propeptides of
Naidu declares conflict of interest. All other authors have no conflict type I collagen indicate low bone mineral density in elderly
of interest. women. Bone 23:471–477
24. Gertz BJ, Clemens JD, Holland SD et al (1998) Application of
a new serum assay for type i collagen cross-linked N-
telopeptides: assessment of diurnal changes in bone turnover
References
with and without alendronate treatment. Calcif Tissue Int
63:102–106
1. Melton U, Chrischilles EA, Cooper C et al (1992) How many 25. Clemens JD, Herrick MV, Singer FR et al (1997) Evidence that
women have osteoporosis? J Bone Miner Res 7:1005–1010 serum NTx (collagen-type I N-telopeptides) can act as an
2. Melton LJ 3rd, Atkinson EJ, O’Connor MK et al (1998) Bone immunochemical marker of bone resorption. Clin Chem
density and fracture risk in men. J Bone Miner Res 13:1915 43:2058–2063
3. Collins JA, Blake JM, Crosignani PG (2005) Breast cancer risk 26. Prestwood KM, Thompson DL, Kenny AM et al (1999) Low dose
with postmenopausal hormonal treatment. Hum Reprod Update estrogen and calcium have an additive effect on bone resorption in
11:545–560 older women. J Clin Endocrinol Metab 84:179–183
4. Herrington DM, Howard TD (2003) Hormone therapy and heart 27. Rosen HN, Parker RA, Greenspan SL et al (2004) Evaluation of
disease: from presumed benefit to potential harm. N Engl J Med ability of biochemical markers of bone turnover to predict a
349:5519–5521 response to increased doses of HRT. Calcif Tissue Int 74:415–
5. Makins R, Ballinger A (2003) Gastrointestinal side effects of 423
drugs. Expert Opin Drug Safety 2:421–429 28. Ton FN, Gunawardene SC, Lee H et al (2005) Effects of low-
6. Kawakami H (2005) Biological significance of milk basic protein dose prednisone on bone metabolism. J Bone Miner Res 20:464–
(MBP) for bone health. Food Sci Technol 11:1–8 470
7. Aoe S, Toba Y, Yamamura J et al (2001) Controlled trial of the 29. Greenspan SL, Parker R, Ferguson L et al (1998) Early
effects of milk basic protein (MBP) supplementation on bone changes in biochemical markers of bone turnover predict the
metabolism in healthy adult women. Biosci Biotechnol Biochem long-term response to alendronate therapy in representative
65:913–918 elderly women: a randomized clinical trial. J Bone Mineral
8. Yamamura J, Aoe S, Toba Y et al (2002) Milk basic protein Res 13:1431–1438
(MBP) increases radial bone mineral density in healthy adult 30. Garnero P, Shih WJ, Gineyts E et al (1994) Comparison of new
women. Biosci Biotechnol Biochem 66:702–704 biochemical markers of bone turnover in late postmenopausal
9. Morita Y, Matsuyama H, Serizawa A et al (2008) Identification of osteoporotic women in response to alendronate treatment. J Clin
angiogenin as the osteoclastic bone resorption-inhibitory factor in Endocrinol Metab 79:1693–1700
bovine milk. Bone 42:380–387 31. Reid IR, Lucas J, Wattie D et al (2005) Effects of a β-blocker
10. Glowacki J (1998) Angiogenesis in fracture repair. Clin Orthop on bone turnover in normal postmenopausal women: a
355S:S82–S89 randomized controlled trial. J Clin Endocrinol Metab 90:5212–
11. Carano RAD, Filvaroff E (2003) Angiogenesis and bone repair. 5216
Drug Discov Today 8:980–989 32. Chen P, Satterwhite JH, Licata AA et al (2005) Early changes in
12. Cornish J, Callon KE, Naot D et al (2004) Lactoferrin is a potent biochemical markers of bone formation predict BMD response to
regulator of bone cell activity and increases bone formation in teriparatide in postmenopausal women with osteoporosis. J Bone
vitro. Endocrinology 145:4366–4374 Miner Res 20:962–970
13. Naot D (2005) Lactoferrin: a novel bone growth factor. Clin Med 33. Suzuki YA, Lonnerdal B (2002) Characterization of mammalian
Res 3:93–101 receptors for lactoferrin. Biochem Cell Biol 80:75–80
14. Naidu AS (2008) Angiogenin complexes (ANGex) and uses 34. Grey A, Banovic T, Zhu Q et al (2004) The low-density
thereof. US Patent Application No. 20080255340 lipoprotein receptor-related protein 1 is a mitogenic receptor for
15. Naidu AS (2008) Immobilized angiogenin mixtures and uses lactoferrin in osteoblastic cells. Mol Endocrinol 18:2268–2278
thereof. US Patent Application No. 20080254018 35. Shestenko OP, Nikonov SD, Mertvetsov NP (2001) Angiogenin
16. Gomez B Jr, Ardakani S, Ju J et al (1995) Monoclonal antibody and its functions in angiogenesis. Mol Biol 35:294–314
assay for measuring bone-specific alkaline phosphatase activity in 36. Chesnut CH III, McClung MR, Ensrud KE et al (1995)
serum. Clin Chem 41(11):1560–1566 Alendronate treatment of the postmenopausal osteoporotic wom-
17. Delmas PD, Stenner D, Wahner HW et al (1983) Assessment of an: effect of multiple dosages on bone mass and bone remodeling.
bone turnover in postmenopausal osteoporosis by measurement of Am J Med 99:144–152
serum bone gla-protein. J Lab Clin Med 102:470–476 37. Ettinger B, Black DM, Mitlak BH et al (1999) Reduction of
18. Clemens JD et al (1997) Evidence that serum NTx (collagen type vertebral fracture risk in postmenopausal women with osteoporosis
I N-telopeptides) can act as immunochemical marker of bone treated with raloxifene: results from a 3-year randomized clinical
resorption. Clin Chem 43:2058–2063 trial. JAMA 282:637–645
19. Delmas PD, Schlemmer A, Gineyts E et al (1991) Urinary 38. Lufkin EG, Whitaker MD, Nickelsen T et al (1998) Treatment of
excretion of pyridinoline crosslinks correlates with bone turnover established postmenopausal osteoporosis with raloxifene: a ran-
measured in iliac crest biopsy in patients with vertebral osteopo- domized trial. J Bone Miner Res 13:1747–1754
rosis. J Bone Miner Res 6:639–644 39. Meunier PJ, Slosman DO, Delmas PD et al (2002) Strontium
20. Heinegard D, Tiderstrom G (1973) Determination of serum ranelate: dose-dependent effects in established postmenopausal
creatinine by a direct colorimetric method. Clin Chim Acta vertebral osteoporosis—a 2-year randomized placebo controlled
43:305 trial. J Clin Endocrinol Metab 87:2060–2066
9. Osteoporos Int
40. Jamal SA, Cummings SR, Hawker GA (2004) Isosorbide mononitrate parathyroid hormone (1–34) for two years and relevance to
increases bone formation and decreases bone resorption in postmen- human safety. Toxicol Pathol 30:312–321
opausal women: a randomized trial. J Bone Miner Res 19:1512–1517 44. Hodsman AB, Bauer DC, Dempster DW et al (2005) Parathyroid
41. Cosman F (2006) Anabolic therapy for osteoporosis: parathyroid hormone and teriparatide for the treatment of osteoporosis: a
hormone. Curr Rheumat Rep 8:63–69 review of the evidence and suggested guidelines for its use.
42. Asirvatham S, Sebastian C, Thadani U (1998) Choosing the most Endocr Rev 26:688–703
appropriate treatment for stable angina. Safety considerations. 45. Hochberg MC, Greenspan S, Wasnich RD et al (2002) Changes in
Drug Saf 19:23–44 bone density and turnover explain the reductions in incidence of
43. Vahle JL, Sato M, Long GG et al (2002) Skeletal changes in rats nonvertebral fractures that occur during treatment with antire-
given daily subcutaneous injections of recombinant human sorptive agents. J Clin Endocrinol Metab 87:1586–1592