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1
By 
Indunath . S 
M pharm part 1 
Pharmacy practice 
2 
OSTEOPOROSIS
Contents 
3
Definitions 
Osteoporosis is defined as low bone mass and 
microarchitectral deterioration of bone tissue, leading to 
enh...
Normal bone x osteoporotic 
bone 5
Epidemiology 
In US 8 million women and 2 million men have osteoporosis. 
It occurs more frequently with increasing age as...
Epidemiology of fractures: At least 
1.5 million fractures occurs in each 
year in the US as a consequence of 
osteoporosi...
Etiology and risk factors 
The magnitude and significance of the risk factors varies by 
gender, ethnicity, age, and the d...
Immobility 
Low sun exposure 
Medical problems like Rheumatoid 
arthritis, hyperthyroidism, 
hyperparathyroidism, Cushing’...
PATHOPHYSIOLOGY 
Bone loss due to normal age related changes in 
bone remodelling as well as extrinsic and 
intrinsic fact...
11
Other reasons include 
Calcium deficiency 
Peak bone mass may be 
impaired by inadequate calcium 
intake, leading to incre...
Estrogens deficiency 
cause bone lose by 
a) Activation of new bone 
remodelling site 
b) Exaggeration of the 
imbalance b...
Drug induced 
Glucocortcoid are the most 
common cause of medication 
induced osteoporosis 
Other medication include 
anti...
Vit D deficiency: Vit D deficiency leads to 
compensatory secondary 
hyperparathyroidism and is an important risk 
factor ...
Clinical manifestations 
General : fractures occur after bending, 
lifting, or falling. 
Symptoms : pain, immobility, brui...
Diagnosis 
Conventional radiography 
Dual-energy X-ray 
absorptiometry (DXA) 
Biomarkers 
Quantitative computer 
tomograph...
Non pharmacologic treatment 
Diet changes : For all individuals, a 
well-balanced diet with adequate 
calcium and vitamin ...
Fruits and vegetable containg Mg is 
essential for healthy bone. 
Patients should be educated to avoid 
consuming excessiv...
Social habit changes: 
Smoking causes bone loss and 
increases hip fracture risk by 
several mechanisms such as 
early men...
Excessive alcohol use has been associated 
with low BMD and subsequent fracture in 
some, but not all, studies. 
Malnutrit...
Exercise also enhances calcium and estrogen therapy. 
Excessive exercise in a premenstrual woman, however, can 
lead to am...
Pharmacotherapy 
Two FDA-approved indication for 
osteoporosis medication- prevention and 
treatment. 
There are two main ...
ANTIRESORPTIVE THERAPY 
Calcium 
Vitamin D & its metabolites 
Selective estrogen modulators 
Bisphosphonates 
Calcitonin 
...
BONE FORMATION THERAPY 
Teriparatide (Parathyroid Hormone) 
Strontium 
HMG - CoA Reductase Inhibitors 
(Statins) 
Growth H...
ANTIRESORPTIVE 
THERAPY 
Calcium : adequate calcium intake is considered 
standard for osteoporosis prevention and treatme...
27 
Calcium Preparation Elemental Calcium Content 
Calcium citrate 60 mg/300 mg 
Calcium lactate 80 mg/600 mg 
Calcium glu...
Vitamin D and Its Metabolites 
Vitamin D 400 units with calcium 500 mg 
twice daily increased spine and hip BMD in 
senior...
Bisphosphonates: 
MOA: It binds to the hydroxyapatite in bone, 
they decrease resorption by inhibiting osteoclast 
adheren...
Selective Estrogen Receptor Modulators 
(SERM) 
Raloxifene - the first SERM approved for 
prevention and treatment of post...
Calcitonin 
Calcitonin is released from the thyroid gland 
when serum calcium is elevated. 
Salmon calcitonin is used clin...
Estrogen and Hormonal Therapy 
Estrogens : 
decrease osteoclast recruitment and activity. 
inhibit PTH peripherally. 
incr...
decrease the activity of the OPG/RANK/RANKL 
pathway, inhibiting bone resorption. 
Response to estrogen deficiency and rep...
Phytoestrogens 
The isoflavonoids (soy proteins) and lignans (flaxseed) are the 
most common forms of phytoestrogens. 
Bon...
Testosterone, in various salt forms, was associated with 
increased BMD in some studies when given to hypogonadal 
men and...
BONE FORMATION 
THERAPY 
Teriparatide (Parathyroid Hormone) 
Therapeutic doses improve BMD and reduce fracture 
risk. 
Par...
Teriparatide is commercially available as a prefilled 3-mL pen 
type delivery device that administers subcutaneous injecti...
HMG-CoA Reductase Inhibitors (Statins) 
These were discovered to increase bone density in 
animal models. 
Although observ...
Growth Hormones and Factors 
Growth hormone (GH) and IGF-1 
play important roles in bone turnover 
and remodeling, with mu...
Investigational Agents 
Osteoprotegerin (OPG), a competitive 
inhibitor of RANKL, blocks osteoclastic 
differentiation and...
Vertebroplasty and kyphoplasty 
The percutaneous injection of 
polymethylmethacrylate (PMMA) bone cement 
into a compresse...
vertebroplas 
ty 42
Kyphoplasty is a 
newer procedure that 
requires drilling into 
the vertebral body 
and inflating a 
balloon to re-expand ...
Special population 
Women with amenorrhea 
For those with amenorrhea or anorexia, higher calcium 
intakes of 1200 to 1500 ...
Men 
Neither estrogens nor SERMs are used. 
Lifestyle modifications 
Bisphosphonates are the drugs of first choice. 
Altho...
Seniors 
Adequate calcium and vitamin D intake should be 
assured. 
For most seniors, bisphosphonates are the preferred 
a...
Transplant recipient 
Before transplant, BMD should be measured and 
vitamin D and gonadal status assessed. 
Bone-healthy ...
HIV/AIDS 
Current data suggest that both the virus and its medical 
treatments can decrease BMD. 
Standard treatment, usua...
Conclusion 
Women and men over age 50 should be assessed 
for risk factors. 
Patients with premature or severe osteoporosi...
Reference 
Harrison’s Principle of Internal Medicine ,Vol 
1 by Longo, Fauci Kasper, Hasper, Jamesoli 
Page No: 2268 – 227...
All information were collected 
from various sources, only for 
academic purpose 
51
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Osteoporosis

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Osteoporosis

  1. 1. 1
  2. 2. By Indunath . S M pharm part 1 Pharmacy practice 2 OSTEOPOROSIS
  3. 3. Contents 3
  4. 4. Definitions Osteoporosis is defined as low bone mass and microarchitectral deterioration of bone tissue, leading to enhanced bone fragility and a consequent increase in fracture risk. World Health organization (WHO) defines Osteoporosis as a bone density that falls 2.5 standard deviations (SD) below the mean for young healthy adults of the same race and gender— also referred to as a T-score of –2.5. 4
  5. 5. Normal bone x osteoporotic bone 5
  6. 6. Epidemiology In US 8 million women and 2 million men have osteoporosis. It occurs more frequently with increasing age as bone tissue is progressively lost. One in three women and one in 12 men over the age of 50 worldwide are estimated to have osteoporosis. 7% of postmenopausal women had osteoporosis. The prevalence of osteoporosis among American subgroup are  Non Hispanic white women: 20%  Mexican American women: 10%  Non Hispanic black women: 5%  Men of all ages: 6% 6
  7. 7. Epidemiology of fractures: At least 1.5 million fractures occurs in each year in the US as a consequence of osteoporosis. In US and Europe, osteoporosis related fractures are more among women than men. 3 lakh hip fracture,7 lakh vertebral fracture and 250,000 wrist fracture occur each year in the US. Multiple fractures lead to height loss, kyphosis, secondary pain 7
  8. 8. Etiology and risk factors The magnitude and significance of the risk factors varies by gender, ethnicity, age, and the duration of risk factor presence. 4 major risk factors age, low BMD, gender, Family history. The other factors that can contribute to osteoporosis are Sedentary life style Low body weight Cigarette and excessive alcohol use Low calcium intake & malnutrition Estrogen deficiency 8
  9. 9. Immobility Low sun exposure Medical problems like Rheumatoid arthritis, hyperthyroidism, hyperparathyroidism, Cushing’s syndrome3, dementia, parkinsonism Medications like immunosuppressant, diuretics, cancer chemotherapy, aluminums, glucocorticoids etc. 9
  10. 10. PATHOPHYSIOLOGY Bone loss due to normal age related changes in bone remodelling as well as extrinsic and intrinsic factors that exaggerate this process. Bone remodelling has two primary functions: To repair micro damage within the skeleton to maintain skeletal strength. To supply calcium supply from the skeleton to maintain serum calcium. After age 30 to 45,the resorption and formation processes become imbalanced, and resorption exceeds formation. Excessive bone loss can be loss due to an increase in osteoclastic activity and/or osteoblastic activity. 10
  11. 11. 11
  12. 12. Other reasons include Calcium deficiency Peak bone mass may be impaired by inadequate calcium intake, leading to increased risk of osteoporosis. It induce secondary hyperparathyroidism and an increase in the rate of remodelling to maintain normal serum calcium levels. 12
  13. 13. Estrogens deficiency cause bone lose by a) Activation of new bone remodelling site b) Exaggeration of the imbalance b/w bone formation and resorption 13
  14. 14. Drug induced Glucocortcoid are the most common cause of medication induced osteoporosis Other medication include anticonvulsant and immunosuppressant 14
  15. 15. Vit D deficiency: Vit D deficiency leads to compensatory secondary hyperparathyroidism and is an important risk factor for osteoporosis and fractures. Physical inactivity: Prolonged bed rest and paralysis, results in significant bone loss. Chronic disease : Disease associated with an increased risk of osteoporosis in adult are turner syndrome, Cushing's syndrome, DM 1,thyrotoxicosis, malnutrition, pernicious anaemia, pregnancy and lactation. Cigarettes consumption : over a long period has detrimental effect on bone mass. These effects may be mediated directly, by toxic effects on osteoblasts, or indirectly by modifying estrogen metabolism. 15
  16. 16. Clinical manifestations General : fractures occur after bending, lifting, or falling. Symptoms : pain, immobility, bruising, depression and lower self esteem. Signs : Shortened stature, Kyphosis, or Lordosis, Bone pain or fracture(commonly of vertebra ,hip or forearm). 16
  17. 17. Diagnosis Conventional radiography Dual-energy X-ray absorptiometry (DXA) Biomarkers Quantitative computer tomography Ultrasound 17
  18. 18. Non pharmacologic treatment Diet changes : For all individuals, a well-balanced diet with adequate calcium and vitamin D is essential for healthy bones. Calcium contributors - Dairy products like milk, yogurt, cheese, ice cream, cottage cheese, and fortified orange juice or soy products. Most vitamin D comes from sun-induced skin conversion Vitamin D contributors - fatty fish, few unfortified foods 18
  19. 19. Fruits and vegetable containg Mg is essential for healthy bone. Patients should be educated to avoid consuming excessive amounts of Vit A.it have increased risk of fracture in both men and women. Vitamin C influences collagen production, and increases osteoblast formation and survival. Moderate protein intake is recommended. Caffeine and Hypophosphatemia decreases the BMD. 19
  20. 20. Social habit changes: Smoking causes bone loss and increases hip fracture risk by several mechanisms such as early menopause decreased body weight enhanced estrogen metabolism increased PTH concentrations decreased vitamin concentrations. 20
  21. 21. Excessive alcohol use has been associated with low BMD and subsequent fracture in some, but not all, studies. Malnutrition associated with alcoholism could also play a role. Alcohol use also may increase the risk of falls. Exercise : Long-term exercise during youth increases peak BMD. Physical activity, especially aerobics, weight bearing, and resistance exercise and walking preserves BMD . 21
  22. 22. Exercise also enhances calcium and estrogen therapy. Excessive exercise in a premenstrual woman, however, can lead to amenorrhea and estrogen deficiency with consequent bone loss and increased fracture risk. Prevention of fall : Ambulation-assistive devices (canes and walkers) and Assistance. The living environment should be evaluated and modified. the use of hip protectant. Medications should be reviewed . Vision should be assessed. Proper lightening. 22
  23. 23. Pharmacotherapy Two FDA-approved indication for osteoporosis medication- prevention and treatment. There are two main classes of drugs. Anti- resorptive therapy - Prevents remodeling. Bone formation Therapy - Improves bone formation. Newer procedures – Vertebroplasty & Kyphoplasty 23
  24. 24. ANTIRESORPTIVE THERAPY Calcium Vitamin D & its metabolites Selective estrogen modulators Bisphosphonates Calcitonin Estrogen & hormonal therapy Tibolone Phytoestrogen Testosterone and Anabolic Steroids 24
  25. 25. BONE FORMATION THERAPY Teriparatide (Parathyroid Hormone) Strontium HMG - CoA Reductase Inhibitors (Statins) Growth Hormones and Factors Fluoride 25
  26. 26. ANTIRESORPTIVE THERAPY Calcium : adequate calcium intake is considered standard for osteoporosis prevention and treatment for all people. Dose 200 – 1500 mg / day. Adr include gas, upset stomach, rare kidney stones. Drug interaction: absorption decreased with PPI, decrease absorption of alendronate, etidronate, fluoride, tetracycline and phenytoin, induce hypercalcemia with diuretics. 26
  27. 27. 27 Calcium Preparation Elemental Calcium Content Calcium citrate 60 mg/300 mg Calcium lactate 80 mg/600 mg Calcium gluconate 40 mg/500 mg Calcium carbonate 400 mg/g Calcium carbonate+ 5g vitamin D2 (OsCal 250) 250 mg/tablet
  28. 28. Vitamin D and Its Metabolites Vitamin D 400 units with calcium 500 mg twice daily increased spine and hip BMD in seniors with vitamin D deficiency. Vitamin D maintain muscle function & decreasing pain. Orally administered vitamin D3, in a dosage of 100,000 units once every 4 months for 5 years, reduced the risk of fracture by 22% to 33% in a population of men and women. Doxercalciferol (1α-hydroxyvitamin D2) is under investigation for osteoporosis treatment. 28
  29. 29. Bisphosphonates: MOA: It binds to the hydroxyapatite in bone, they decrease resorption by inhibiting osteoclast adherence to bone surfaces. Etidronate - inhibit bone mineralization that could lead to osteomalacia. Alendronate(5mg daily) postmenopausal Risedronate(5mg daily) osteoporosis Ibandronate (2.5mg/day) Risedronate -glucocorticoid-induced osteoporosis Alendronate - glucocorticoid-induced & osteoporosis in men 29
  30. 30. Selective Estrogen Receptor Modulators (SERM) Raloxifene - the first SERM approved for prevention and treatment of postmenopausal osteoporosis, is an estrogen agonist in bone tissue but an antagonist in the breast and uterus. Tamoxifen approved for breast cancer prevention, also inhibits bone loss. Investigational SERM - Arzoxifene, bazedoxifene, lasofoxifene, and ospemifene 30
  31. 31. Calcitonin Calcitonin is released from the thyroid gland when serum calcium is elevated. Salmon calcitonin is used clinically because it is more potent and longer lasting than the mammalian form. Calcitonin (200 units daily, intranasally every other day) is indicated for osteoporosis treatment for women at least 5 years past menopause. Calcitonin may provide pain relief to some patients with acute vertebral fractures, but this effect is minimal. 31
  32. 32. Estrogen and Hormonal Therapy Estrogens : decrease osteoclast recruitment and activity. inhibit PTH peripherally. increase calcitriol conc. and intestinal Ca absorption. decrease renal calcium excretion. decrease cytokine concentrations . 32
  33. 33. decrease the activity of the OPG/RANK/RANKL pathway, inhibiting bone resorption. Response to estrogen deficiency and replacement may be related to estrogen receptors and polymorphisms. Hormonal therapy (HT) was shown to decrease vertebral, hip, and all fractures by 34%, 34%, and 24% respectively. Tibolone Tibolone, a synthetic steroid, and its metabolites are weak estrogen-, progesterone-, and androgen-receptor agonists. They relieve hot flushes and increase BMD, but have no effect on the endometrium. 33
  34. 34. Phytoestrogens The isoflavonoids (soy proteins) and lignans (flaxseed) are the most common forms of phytoestrogens. Bone effects may be related to bone estrogen receptor agonist activity or potentially direct or indirect effects on osteoblasts and osteoclasts. Testosterone and Anabolic Steroids In a few studies, women receiving methyl testosterone 1.25 or 2.5 mg oral daily or testosterone implants 50 mg every 3 months had increased BMD. 34
  35. 35. Testosterone, in various salt forms, was associated with increased BMD in some studies when given to hypogonadal men and senior men with normal hormone levels or mild hormonal deficiency. Transdermal gel, oral, intramuscular, and pellet testosterone products are available. 35
  36. 36. BONE FORMATION THERAPY Teriparatide (Parathyroid Hormone) Therapeutic doses improve BMD and reduce fracture risk. Parathyroid hormone is currently the only approved osteoporosis medication that works by stimulating bone formation. Teriparatide works equally well in women and men with osteoporosis. Teriparatide : decrease the risk of new vertebral fractures by 65% with osteoporosis and pre-existing fractures & non vertebral fracture risk by 53% with the 20-mcg/day in dosage 36
  37. 37. Teriparatide is commercially available as a prefilled 3-mL pen type delivery device that administers subcutaneous injections in the thigh or abdominal area. Strontium Strontium stimulates bone formation and decreases bone resorption. strontium ranelate 1 g twice daily or 2 g once daily reduced new vertebral fractures by 41%, and increased lumbar spine BMD by 14% and femoral neck BMD by 8% compared with placebo. 37
  38. 38. HMG-CoA Reductase Inhibitors (Statins) These were discovered to increase bone density in animal models. Although observational studies have linked statin use with decreased fracture risk, a large case-control study did not demonstrate reduction in fracture risk for statin-treated patients Fluoride Although fluoride increases osteoblastic activity and bone formation through intracellular signaling pathways involving tyrosine phosphatases and mitogen-activated protein kinases, it remains an unapproved therapy despite 30 years of clinical study. 38
  39. 39. Growth Hormones and Factors Growth hormone (GH) and IGF-1 play important roles in bone turnover and remodeling, with multiple effects on other tissues. The longer-term studies showed a positive effect that continued to increase for 1 to 2 years after discontinuation of GH therapy. Recombinant IGF-1 injections, with or without IGF-3 binding protein, increased both bone formation and resorption. 39
  40. 40. Investigational Agents Osteoprotegerin (OPG), a competitive inhibitor of RANKL, blocks osteoclastic differentiation and has decreased bone resorption biomarkers (phase I and II). Agents to block osteoclast attachment, inhibit bone matrix degradation , or change osteoclast cell structure have been initially effective. 40
  41. 41. Vertebroplasty and kyphoplasty The percutaneous injection of polymethylmethacrylate (PMMA) bone cement into a compressed vertebral fracture confers significant pain relief for many patients. Under local anesthetic, with computed tomography scanning or fluoroscopic guidance, PMMA is injected under slight pressure during vertebroplasty. The procedure stabilizes the damaged vertebrae and reduces pain in 70% to 92% of patients. Pain scores usually improve by approximately 50% at 1 month following the treatment. 41
  42. 42. vertebroplas ty 42
  43. 43. Kyphoplasty is a newer procedure that requires drilling into the vertebral body and inflating a balloon to re-expand the fracture. The process is followed by the injection of about 7 mL of the PMMA cement. 43
  44. 44. Special population Women with amenorrhea For those with amenorrhea or anorexia, higher calcium intakes of 1200 to 1500 mg and adequate vitamin D are recommended. In anorexia, the primary therapy is normal diet, weight gain, and return of normal menses. The American Academy of Pediatrics recommends low-dose estrogen supplementation for amenorrhea if age is greater than 16 until normal menses returns 44
  45. 45. Men Neither estrogens nor SERMs are used. Lifestyle modifications Bisphosphonates are the drugs of first choice. Although alendronate is FDA-approved for men and reduces the risk of vertebral fractures, other available bisphosphonates are also clinically used. Osteoporosis due to secondary causes should include treatment of the underlying cause plus a bisphosphonate. 45
  46. 46. Seniors Adequate calcium and vitamin D intake should be assured. For most seniors, bisphosphonates are the preferred agents. Raloxifene, nasal calcitonin, or parenteral teriparatide are treatment options for seniors who will not or cannot take an oral bisphosphonate. Arthritis Patients taking glucocorticoids should be managed with calcium and vitamin D supplementation plus a bisphosphonate. Otherwise, standard osteoporosis prevention and treatment interventions 46
  47. 47. Transplant recipient Before transplant, BMD should be measured and vitamin D and gonadal status assessed. Bone-healthy lifestyle changes and therapy should be instituted as needed and hypogonadism corrected before and after transplant. Intermittent Pamidronate has decreased bone loss in most transplant recipients. Diabetes Testosterone may cause hypoglycemia. Although one study with alendronate documented decreased insulin requirements, further data are needed. 47
  48. 48. HIV/AIDS Current data suggest that both the virus and its medical treatments can decrease BMD. Standard treatment, usually consisting of a bisphosphonate plus calcium and vitamin D supplementation, should be used once osteoporosis is diagnosed, although no specific population data yet exist. Cystic fibrosis Prevention and treatment efforts usually include adequate Calcium and vitamin D intake. Correction of hypogonadism. Exercise. Reductions in glucocorticoid use. 48
  49. 49. Conclusion Women and men over age 50 should be assessed for risk factors. Patients with premature or severe osteoporosis should be evaluated for secondary causes of bone loss. Male osteoporosis is often secondary to specific diseases and drugs. Bisphosphonates are the cornerstone for osteoporosis treatment. Raloxifene is an alternative treatment option to prevent vertebral fractures. All people, regardless of age, should incorporate a healthy lifestyle beginning at birth that emphasizes regular exercise, nutritious diet, and tobacco avoidance to prevent and treat osteoporosis 49
  50. 50. Reference Harrison’s Principle of Internal Medicine ,Vol 1 by Longo, Fauci Kasper, Hasper, Jamesoli Page No: 2268 – 2277,18 th edition Pharmacotherapy- A path physiological approach, by Joseph. T. Dipiro, Robert. L. Talbert, Gary. C. Yee, Gary. R. Matzke , Barbara. G. Wells, L. Michael Posey; Page No: 1645 – 1664 ,6 th edition. 50
  51. 51. All information were collected from various sources, only for academic purpose 51

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