. Bone Remodeling in Basic Multicellular Units and Bone Modeling by Osteoblasts and Osteoclasts. During growth, chondrocytes mature and direct the formation of new bone trabeculae in the process of endochondral bone formation, and osteoblasts form new bone by periosteal appositional growth. These processes determine the length and width of bones. Bone is remodeled by osteoclasts (bone-resorbing cells) coupled with osteoblasts (bone-forming cells) in basic multicellular units. Bone remodeling is necessary to maintain calcium homeostasis and to renew bone to repair microdamage and microcracks. The shape of bone is determined by the modeling conducted by uncoupled osteoblasts and osteoclasts.
Osteoporosis by dr.arun
Pathogenesis of osteoporosis
Definition:Metabolic bone disease categorized by histology :Osteoporosis OsteomalaciaDecrease in matrix Bone matrix intactand mineral. reduced mineral.Osteoporosis defintion by NIH ConsensusConference, 2000: Skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture. Bone strength= Bone density + Bone quality1
Regulation of bone remodeling. Signals that determine the differentiation, function, and death of these cells and their progenitors determine how many units are activated over time, how active and well-balanced the basic multicellular unit is, and whether, at the end of the cycle, bone mass will be gained, lost, or stable4Canalis E et al. N Engl J Med2007;357:905-916
Systemic hormones involved:• Parathyroid hormone - is the most important regulator of calcium homeostasis. It maintains serum calcium concentrations by: Stimulating bone resorption Increasing renal tubular calcium reabsorption Increasing renal calcitriol production.PTH stimulates bone formation when given intermittently, but inhibits collagen synthesis at high concentrations 26,27. It stimulates osteoclast mediated bone resorption when given (or secreted) continuously. It also stimulates gene expression and increases the production of several local factors, including IL-6, IGF-1 and an IGF-binding protein, IGF-BP-5, and prostaglandins. 28,37. Canalis E et al. N Engl J Med 2007;357:905-916
Calcitriol : increases intestinal calcium and phosphorus absorption, thereby promoting bone mineralization. At high concentrations, under conditions of calcium and phosphate deficiency, it also stimulates bone resorption, thereby helping to maintain the supply of these ions to other tissues. Calcitonin : inhibits osteoclasts and therefore bone resorption in pharmacologic doses. However, its physiologic role is minimal in the adult skeleton. Its effects are transient, probably because of receptor downregulation. Growth hormone and IGFs : The GH/IGF-1 system and IGF-2 are important for skeletal growth, especially growth at the cartilaginous end plates and endochondral bone formation.
Osteoporotic bone showing loss of bone with larger spaces decreasing its strength .2
Clinical risk factors: Ebeling P. N Engl J Med 2008;358:1474-1482
BMD measurement: 1. Dual-Energy X-Ray Absorptiometry: Results expressed as • T-SCORE is the number of SD the measurement is above or below the YOUNG-NORMAL MEAN BMD. • Z-SCORE is the number of SD the measurement is above or below the AGE-MATCHED MEAN BMD. Sites used for measurement per WHO criteria: •Total proximal femur •Femoral neck •Lumbar spine •33percent(1/3rd)radius if e/o OA or surgery at other 3 sites. Peripheral skeletal sites predict global # risk, however not used in WHO/FRAX criteria therefore limited value. Changes to therapy atRaisz L. N Engl J Med 2005;353:164-171 these sites are slow.
WHO diagnostic categories of BMDEbeling P. N Engl J Med 2008;358:1474-1482
Other lab tests: Initial laboratory tests :• Complete chemistry profile (including alkaline phosphatase)• CBC• Calcium, phosphorus• 25 hydroxyvitamin D• Urinary calcium excretion Additional laboratory tests if indicated(clinical features/ low Z-score)• 24 hour urine for free cortisol• Estradiol, FSH, LH, Prolactin , TSH• Magnesium• 1,25 dihydroxyvitamin D ,Intact PTH• Celiac screen• SPEP/UPEP• ESR, Rheumatoid Factor• Serum tryptase and histamine levels• Homocysteine• Skin biopsy for connective tissue disorders• COL1A genetic testing for osteogenesis imperfecta• Serum and urine markers of bone turnover
IN THE INTESTINEIt facilitates intestinal absorption of calcium, aswell as stimulates absorption of phosphate andmagnesium ions.In the absence of vitamin D, dietary calcium is notabsorbed at all efficiently.Vitamin D stimulates the expression of a numberof proteins involved in transporting calcium fromthe lumen of the intestine, across the epithelialcells and into blood.
The vitamin D form, 1,25-dihydroxcholecalciferol [1,25(OH)2D3],• 1. stimulates the synthesis of the epithelial calcium channels in the plasma membrane calcium pumps , and• 2. induces the formation of the calbindins.
Calcitriol Raises Blood Calcium in 3 Ways:1. Increases Ca++ absorption by the small intestine.2. Increases Calcium (and Phosphate ) resorption from the skeleton. It binds to hematopoietic stem cells and causes differentiation of osteoclasts.3. Weakly promotes the reabsorption of Calcium ions by the kidney cells (less calcium excreted)
Vitamin D has also been shown to play an important part in regulating the proliferation and differentiation of both types of bone remodeling cells - those responsible for bone breakdown and those that reform the bone anew…and more.•
Parathyroid Gland Anatomy• Four Parathyroid glands are usually found posterior to the thyroid gland• Total weight of parathyroid tissue is about 150mg• Parathyroid hormone (PTH) is made by these glands
Low Blood Calcium Parathyroid gland releases parathyroid hormone Stimulates osteoclasts to resorb Ca++ Blood calcium rises Promotes the final step of Calcitriol synthesis by kidneys Feedback Inhibition High Blood Calcium Inhibits parathyroid gland