Osteomalacia

Osteomalacia is caused by deficiency of vitamin D. Vitamin D regulates calcium homeostasis in the body by facilitating absorption of calcium from the intestine and, together with PTH, by enhancing calcium mobilization from bone and by reducing excretion of calcium by the kidney. Deficiency of vitamin D leads to inadequate absorption of calcium. Low levels of calcium stimulate the release of PTH, which in turn causes release of calcium from bone and failure to mineralize newly formed bone. 

Osteomalacia in childhood is known as ricketts and leads to soft bones with characteristic deformities. In adults there is generalized reduction in mineralization of bone matrix and symptoms of bone pain and tenderness. 

Nutritional rickets results from inadequate exposure to sunlight or deficiency of vitamin D. 

Metabolic rickets and osteomalacia result from abnormality in synthesis of or response to calcitriol, the active form of vitamin D. 

Some drugs, for example anticonvulsants phenytoin, phenobarbital and corticosteroids can lead to osteomalacia and rickets by depressing vitamin D dependent calcium uptake in the intestine. 

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Vitamin Dj has m.p. 115-117°C and D, m.p. 82 83 "C. Both vitamins, which have almost identical actions, are used for the prevention and cure of infantile rickets they are essential for the normal development of teeth, and are used for treating osteomalacia and dental caries. They are necessary for the absorption of Ca and P from the gut. 

Other Calcium Disorders. In addition to hypocalcemia, tremors, osteoporosis, and muscle spasms (tetary), calcium deficiency can lead to rickets, osteomalacia, and possibly heart disease. These, as well as Paget s disease, can also result from faulty utilization of calcium. Calcium excess can lead to excess secretion of calcitonin, possible calcification of soft tissues, and kidney stones when combined with magnesium deficiency. 

Phosphorus Disorders. Phosphoms nutrient deficiency can lead to rickets, osteomalacia, and osteoporosis, whereas an excess can produce hypocalcemia. Faulty utilisation of phosphoms results in rickets, osteomalacia, osteoporosis, and Paget s disease, and renal or vitamin D-resistant rickets. 

In certain diseases, such as osteomalacia, syphilis, and osteomyeHtis, bones break spontaneously and without a trauma. The severity of the fracture usually depends on the force that caused the fracture. If a bone s breaking point was exceeded only slightly, then the bone may crack rather than break all the way through. If the force is extreme, such as in an automobile collision or a gunshot, the bone may shatter. An open or compound fracture is particularly serious because infection is possible in both the wound and the bone. A serious bone infection can result in amputation. 

Clinical stresses which interfere with vitamin metabohsm, can result in calcium deficiency leading to osteomalacia and osteoporosis (secondary vitamin D deficiency). These stresses include intestinal malabsorption (lack of bile salts) stomach bypass surgery obstmctive jaundice alcoholism Hver or kidney failure decreasing hydroxylation of vitamin to active forms inborn error of metabohsm and use of anticonverdiants that may lead to increased requirement. 

H. M. Frost, Bone Dynamics in Osteoporosis and Osteomalacia Surgery Monograph Series, Charles C. Thomas, Pubhsher, Springfield, HI., 1966. 

Primary hyperparathyroidism occurs as a result of hyperplasia or the occurrence of adenoma. Secondary hyperparathyroidism may result from renal failure because of the associated phosphate retention, resistance to the metabolic actions of PTH, or impaired vitamin D metabolism. The last-mentioned factor is primarily responsible for the development of osteomalacia. Muscle symptoms are much more common in patients with osteomalacia than in primary hyperparathyroidism. Muscle biopsy has revealed disseminated atrophy, sometimes confined to type 2 fibers, but in other cases involving both fiber types. Clinical features of osteomalacic myopathy are proximal limb weakness and associated bone pain the condition responds well to treatment with vitamin D. 

D Calciferol Maintenance of calcium balance enhances intestinal absorption of Ca and mobilizes bone mineral Rickets = poor mineralization of bone osteomalacia = bone demineralization... 

Vitamin D is not strictly a vitamin since it can be synthesized in the skin, and under most conditions that is its major source. Only when sunlight is inadequate is a dietary source required. The main function of vitamin D is in the regulation of calcium absorption and homeostasis most of its actions are mediated by way of nuclear receptors that regulate gene expression. Deficiency—leading to rickets in children and osteomalacia in adults—continues to be a problem in northern latitudes, where sunlight exposure is poor. 

In the vitamin D deficiency disease rickets, the bones of children are undermineralized as a result of poor absorption of calcium. Similar problems occur in adolescents who are deficient during their growth spurt. Osteomalacia in adults results from demineralization of bone in women who have little exposure to sunlight, often after several pregnancies. Although vitamin D is essential for prevention and treatment of osteomalacia in the elderly, there is little evidence that it is beneficial in treating osteoporosis. 

Vitamin A (retinol), present in carnivorous diets, and the provitamin (P-carotene), found in plants, form retinaldehyde, utilized in vision, and retinoic acid, which acts in the control of gene expression. Vitamin D is a steroid prohormone yielding the active hormone derivative calcitriol, which regulates calcium and phosphate metaboUsm. Vitamin D deficiency leads to rickets and osteomalacia. 

The basic clinical tool used at the present time Is the competitive ligand binding assay for 25-OH-D. Although concentrations are low In the serum of patients with osteomalacia and v . tamln D deficiency rickets, we have recently noted the Interesting paradox that levels can be only 1/2 normal In the face of oyert bone disease (32). This had led us to propose that substrate levels of 25-OH-D3 available to the hydroxylase In kidney which Is responsible for the conversion of 25-OH-D3 to the tissue active metabolite, l,25(OH)2D3, may be rate limiting for this enzyme. 

Aluminium toxicity is the likely cause of three human disorders arising from long-term haemodialysis vitamin D-resistant osteomalacia, iron adequate microcytic anaemia, and dialysis dementia (Martin, 1994). The first of these conditions is consistent with interference with calcium deposition into bone, and the accumulation of aluminium in the bone matrix. 

Rashes may occur in 10% of patients. Other side effects include hepatitis, osteomalacia, cardiac conduction defects, and lupus-like reactions. 

Common but usually transient side effects are lethargy, incoordination, blurred vision, higher cortical dysfunction, and drowsiness. At concentrations greater than 50 mcg/mL, phenytoin can exacerbate seizures. Chronic side effects include gingival hyperplasia, impaired cognition, hirsutism, vitamin D deficiency, osteomalacia, folic acid deficiency, carbohydrate intolerance, hypothyroidism, and peripheral neuropathy. 

The major manifestation of chronic metabolic acidosis is bone demineralization with the development of rickets in children and osteomalacia and osteopenia in adults. 

ROD progresses insidiously for several years before the onset of symptoms such as bone pain and fractures. Skeletal complications include osteitis fibrosa cystica (high bone turnover), osteomalacia (low bone turnover) and adynamic bone disease. When ROD symptoms appear, the disease is not easily amenable to treatment. 

Chronic hypophosphatemia can cause osteopenia and osteomalacia because of enhanced osteoclastic resorption of bone. 

Osteoporosis, decrease in bone mass, and osteomalacia, decrease in bone mineralization, may occur in aging humans, sometimes concurrently within the same individual. Various nutritional, hormonal, iatrogenic, physical and circulatory factors have been implicated as influencing bone health (1). ... 

The nutritional experiments with carotene and fish oils led to the conclusion that a second fat-soluble compound was essential for normal rat growth. Rickets, the condition caused by vitamin D deficiency, is a disease afflicting children where, because of impaired calcification, bone formation is disturbed and the bones become bowed and otherwise deformed. In adults, especially multiparous women, vitamin D deficiency produced osteomalacia—demineralization of bone, leading to tenderness over the bones, pain, and muscle weakness. Rickets was particularly prevalent in slum areas. Glasgow, Vienna, and Lahore were notorious for the high incidence of the disease. 

The two hydroxylase enzymes can also utilize the plant-derived steroid, ergocalci-ferol, (vitamin D2) as a substrate. The final product is biologically active and so food manufacturers often fortify their products with ergocalciferol to prevent the occurrence of vitamin D deficiency and consequent rickets in childhood or osteomalacia in adults. 

The GP made a provisional diagnosis of osteomalacia and prescribed vitamin D supplements. Vitamin D measurements are not performed routinely, but the assumption is that a low result would have been obtained on the blood sample. Most of the vitamin D necessary to maintain normal calcium homeostasis is derived from endogenous synthesis by reactions in the skin (which require UV radiation from sunlight), liver and kidney. The cultural habits of Mrs Al-Ameri required her to dress in a burqah and niqab whenever she left the home, meaning that very little of her skin was exposed to daylight. 

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