Discussion: - primary function of 1,25 OH2D3) is to maintain skeletal homeostasis as well as for maintenance of plasma Ca homeostasis; - primary effect of lack of Vit D is decrease in miceralization of newly formed bone matrix (osteoid); - rate of bone formation is decreased; - net result is less total bone & marked change in quality of bone; - only minute amounts of vitamin D are necessary for parathyroid hormone to carry out its actions on bone and kidney; - osteomalacia, group of dz processes characterized by defective mineralizaiton can be caused by any problem resulting in inadequate amounts of Vit D or low plasma PO4; - in osteomalacia defective mineralizaiton results in relative increase in amount of osteoid (unmineralized bone matrix) in bone;

Wheeless' Textbook of Orthopaedics

Sections on - Bone multicellular units Calcium supplements: Calcitonin Differential Dx Estrogen: HyperPTH / HypoPTH HypoCa / HyperCa Hypophosphatemic Vitamin D-resistant rickets Hyperthyroidism MSK Changes Associated w/ Steroids Osteomalacia Osteoporosis, Postmenopausal Pagets Disease Renal Disease: effects on bone Rickets Vit D & Abnormalities Wheeless' Textbook of Orthopaedics

- generalized pathologic processes in bone can be best understood by understanding how these processes alter the normal sequence of bone remodeling as described in the previous chapter; - bone remodeling occurs in local groups of osteoblasts and osteoclasts called bone multicellular units (BMU); - each unit is organized into "cutting cone" of osteoclasts reabsorbing bone followed by trail of osteoblasts reforming the bone to fill defect left by osteoclasts; - end product is a new osteon;

- contraindicated w/ clinical allergy, must periodically examine urine sediment with chronic use; - for symptomatic Paget's Disease of bone, hypercalcemia, post-menopausal osteoporosis (in addition to supplemental calcium, adequate vitamin D intake, and adequate diet);

calcium content of various supplements: - 8 oz of milk: 250-300 mg (and also contains 100 international units of vitamin D); - 1 gm of calcium is present in 2.5 gm of calcium carbonate; - 1 gm of calcium is present in 5.0 gm of calcium citrate; - 1 gm of calcium is present in 8.0 gm of calcium lactate; - 1 gm of calcium is present in 10.0 gm of calcium gluconate; - phoslo - calcium acetate: 667 MG - calcium acetate anhydrous 667 MG = Calcium 169 M - calcium carbonate: - Os-Cal 250 = 625mg calcium carbonate (each tab contains 250mg of elemental calcium and 125 USP units of Vit D); - Os-Cal 500 = 1250 mg calcium carbonate (each tab contains 500mg of elemental calcium); - Os-Cal Forte = 250mg elemental calcium plus vitamins and minerals; - CaCO3 650mg PO tid/qid is good for slowing diarrhea induced by tube feeding; - for calcium replacment: Adults: 500mg PO qd or 1 tab tid; - cal-bid: calcium supplement w/ Vit C and D added - 625 mmg (= 250 mmg elemental calcium);

Wheeless' Textbook of Orthopaedics Discussion: - physical properties - state in body fluids - calcium is a necessary & important addition to cell membranes, giving strength to these structures and regulating permeability; - physiologic roles of calcium are well established; - abnormally low concentrations of Ca permit spontaneous discharges of both sensory & motor fibers in peripheral nerves, leading to tetany; - see depolarization and calcium regulation of muscle contraction; - w/ elevated levels, nerve impulses are blocked, leading to coma; - normal levels: - serum: 4.2-5.3 mEq/L or 8.5-10.5 mg/dL; - ionized: 2.24-2.46 mEq/L or 4.48-4.92 mg/dL

Wheeless' Textbook of Orthopaedics Discussion: - a disorder which is caused by excessive production of parathyroid hormone which leads to hypercalcemia, recurrent nephrolithiasis, pancreatitis, peptic ulcers, and mental changes; - incidence of approx 5 /10,000 pts per year; - usually affects adults over 50 yrs & occurs more commonly in females; - causes: - in most cases is due to single parathyroid adenoma (80% of patients); - malignant tumor: occurs in about 1% of patients with hyperparathyroidism; - occurs often in association w/ multiple endocrine neoplasia syndrome, and rarely to parathyroid carcinoma; - hyperparathyoidism is sometimes seen in renal cell carcinoma and squamous cell carcinoma

Wheeless' Textbook of Orthopaedics Discussion: - most common cause of hypoparathyroidism is inadvertant damage or removal of the parathyroids during surgical removal of the thyroid; - in idiopathic cases, look for ectodermal changes, mental retardation, monilial infections, low Ca; - congenital hypoparathyroid & late onset hypoparathyroidism from other causes in adulthood are rare conditions; - pseudohypoparathyroidism is another cause of this disorder; - end organ unresponsiveness to parathyroid hormone; - patients tend to be short and may have short metacarpals (index, ring, little);

Wheeless' Textbook of Orthopaedics Discussion: - this is the most frequently encountered form of rickets and consists of a genetic or acquired fault in the handling of phosphate in the proximal tubule; - patholophysiology: - decreased reabsorpion of phosphate by the renal tubule (causing hypophosphatemia) (otherwise the renal function is normal, ie BUN and Cr are normal); - decreased absorption of calcium and phosphorous from the GI tract;

Wheeless' Textbook of Orthopaedics Discussion: - physical properties - state in body fluids - physiologic roles of calcium are well established; - abnormally low concentrations of Ca permit spontaneous discharges of both sensory & motor fibers in peripheral nerves, leading to tetany; - w/ elevated levels, nerve impulses are blocked, leading to coma; - calcium is also necessary & important addition to cell membranes, giving strength to these structures and regulating permeability; - sudden death may occur when the ionized calcium falls below 2 mg/dL;

Case series using internal fixation. PubMed Abstract Orthopedics. 2005 Jun;28(6):587-92 Chhabra A, Westerlund LE, Kline AJ, McLaughlin R.

- is a type of metabolic bone disease in which the essential problem is a lack of available calcium or phosphorus (or both) for mineralization of newly formed osteoid; - children w/ rickets & adults w/ osteomalacia present w/ similar findings; Wheeless' Textbook of Orthopaedics

In just 3 years, striking new advances have been made in understanding the molecular mechanisms that govern the crosstalk between osteoblasts/stromal cells and hemopoietic osteoclast precursor cells that leads to osteoclastogenesis. Led first by the discovery of osteoprotegerin (OPG), a naturally occurring protein with potent osteoclastogenesis inhibitory activity, rapid progress was made to the isolation of RANKL, a transmembrane ligand expressed on osteoblasts/stromal cells, that binds to RANK, a transmembrane receptor on hemopoietic osteoclast precursor cells. The interaction of RANK and RANKL initiates a signaling and gene expression cascade that results in differentiation and maturation of osteoclast precursor cells to active osteoclasts capable of resorbing bone. Osteoprotegerin acts as a decoy receptor; it binds to RANKL and blocks its interaction with RANK, thus inhibiting osteoclast development. Many of the calciotropic hormones and cytokines, including vitamin D3, parathyroid hormone, prostaglandin E2 and interleukin-11, appear to stimulate osteoclastogenesis through the dual action of inhibiting production of OPG and stimulating production of RANKL. Estrogen, on the other hand, appears to inhibit production of RANKL and RANKL-stimulated osteoclastogenesis. Recently, the results of the first clinical trial with OPG supported its potential as a therapeutic agent for osteoporosis. The new understanding provided by the RANK/RANKL/OPG paradigm for both differentiation and activation of osteoclasts has had tremendous impact on the field of bone biology and has opened new avenues for development of possible treatments of diseases characterized by excessive bone resorption. from Medscape General Medicine™ Posted 03/08/2000

Wheeless' Textbook of Orthopaedics Discussion: - a chronic progressive disease osteoblasts and osteoclasts which results in abnormal bone remodeling; - etiology, staging, and pathogenesis - prevalence: - uncommon in pts under age of 55 yrs but relatively common in later life, occurring in 3-4% of persons over 55 yrs & occurs in 10% of population over the age of 80 yrs;