Osteomalacia

Osteomalacia is a disorder in which the structural and metabolic functions of the skeleton are impaired because newly formed bone matrix fails to mineralize. It usually results from vitamin D deficiency. Symptoms may include bone pain, myalgias, weakness, and fragility fractures. Diagnosis is with x-rays and serum levels of Ca, phosphate, alkaline phosphatase, parathyroid hormone, and vitamin D. Treatment is directed at the cause, which usually involves giving supplemental vitamin D.

Geriatric Essentials

• Vitamin D deficiency is common in the elderly, particularly those deprived of sunlight (eg, those housebound or in a nursing home) or who have undernutrition.
• Osteomalacia should be suspected in patients with typical ribbonlike cortical lucencies (pseudofractures) that are found with plain x-rays and in patients in whom the serum Ca level is low or low-normal, the serum phosphorus level is low, and the serum alkaline phosphatase and parathyroid hormone levels are high.
• Elderly patients with osteomalacia usually require supplemental vitamin D and Ca.

Osteomalacia (analogous to rickets in children) is relatively rare in the elderly, although deficiency of vitamin D and Ca is common.

Vitamin D is really a prohormone. It can be synthesized in the skin in response to specific wavelengths of ultraviolet light that are in sunlight or it can be obtained in the diet. Dietary sources of vitamin D (eg, fish liver oils, egg yolks, and, in many developed nations, some fortified foods) usually supply only a small portion of the daily requirement, so exposure to sunlight is usually required to maintain adequate vitamin D stores. In people < 70, even brief, limited sun exposure is adequate; however, after age 70, skin conversion becomes less efficient, predisposing to deficiency. Once formed in the skin or ingested, vitamin D is hydroxylated in the liver to 25-hydroxyvitamin D (calcidiol), which is normally present in relatively high concentrations in the circulation and bound to a vitamin D-binding protein. Final activation of vitamin D to the active hormone 1,25-dihydroxyvitamin D (calcitriol) occurs in the kidney by 1-hydroxylase; 1,25-dihydroxyvitamin D stimulates intestinal absorption of Ca and phosphorus, thus promoting bone mineralization.

Etiology

Osteomalacia may result from moderate to severe vitamin D deficiency. Patients with mild to moderate vitamin D deficiency usually have osteoporosis rather than osteomalacia.

Vitamin D deficiency may be caused by inadequate synthesis of vitamin D in patients who get little sun exposure because they live in northern latitudes or are housebound or in a nursing home or because they stay indoors during the winter months. Impairment of small-bowel absorption of dietary vitamin D in elderly patients with fat malabsorption or hypoparathyroidism can also contribute to deficiency.

Impairment of hepatic hydroxylation to 25-hydroxyvitamin D occurs in patients with severe liver disease and in those taking drugs that alter hepatic hydroxylases, especially anticonvulsants such as phenytoin, barbiturates, or carbamazepine. Impairment of conversion to 1,25-dihydroxyvitamin D is commonly due to loss of renal 1-hydroxylase activity in renal failure.

Vitamin D deficiency usually causes hypocalcemia, which stimulates parathyroid hormone (PTH) production, resulting in hyperparathyroidism. Hyperparathyroidism causes increased bone resorption and decreased urinary excretion of Ca, which results in normalization of serum Ca level in most patients with vitamin D deficiency. On the other hand, PTH increases the urinary excretion of phosphate, which, combined with decreased intestinal absorption, causes hypophosphatemia.

Phosphate deficiency (with resulting hypophosphatemia) can cause osteomalacia by impairing bone mineralization. Hypophosphatemia rarely results from inadequate dietary intake, but it can result from impaired absorption (eg, due to malabsorption syndromes or vitamin D deficiency) or from renal losses (eg, due to hyperparathyroidism or congenital disorders of renal phosphate transport). Hypophosphatemia can result from ingesting large amounts of phosphate-binding antacids (eg, aluminum hydroxide). One form of hypophosphatemic osteomalacia, neoplastic or oncogenic osteomalacia, is associated with tumors of mesenchymal origin (such as tumors originating in connective tissue, muscle, or endothelium), but the hypophosphatemia may be due to inhibition of 1-hydroxylase in the kidney.

Ca deficiency very rarely causes osteomalacia.

Symptoms and Signs

Main symptoms of osteomalacia are bone pain, deformities, myalgias, weakness, and fragility fractures. Patients may present with back pain similar to that of osteoporotic vertebral compression fractures. Weakness may be profound in severe osteomalacia and may be attributable to absence of direct stimulatory effects of vitamin D on muscle cell function and to the low levels of Ca and phosphorus.

Diagnosis

In patients with bone pain or deformities, x-rays are done. In these patients and those with unexplained diffuse weakness, levels of serum Ca, phosphorus, alkaline phosphatase, PTH, and 25-hydroxyvitamin D are measured. Patients with osteomalacia may have vertebral compression fractures, mimicking osteoporosis. Incomplete ribbonlike areas of demineralization (eg, pseudofractures, Looser transformation zones, Milkman syndrome) may be visible in the cortex on x-rays of the scapula, pelvis, and long bones. These pseudofractures are nearly pathognomonic for osteomalacia. Patients may also have bowing of the extremities, particularly those with congenital hypophosphatemia. Some patients with congenital hypophosphatemia do not show significant bowing until they are older, but most are diagnosed as children or young adults.

Osteomalacia due to vitamin D deficiency should be suspected when the serum Ca level is low or low-normal, the serum phosphorus level is low, and the serum alkaline phosphatase and PTH levels are high. Vitamin D deficiency is diagnosed by a low 25-hydroxyvitamin D level in the serum; levels in healthy people are 25 to 40 ng/mL (60 to 100 nmol/L). If the diagnosis is unclear, urinary Ca and serum 1,25-dihydroxyvitamin D levels can be measured. Urinary Ca is usually extremely low in vitamin D deficiency. If deficiency is severe, 1,25-dihydroxyvitamin D level is usually low.

In some cases, a bone biopsy is necessary for definitive diagnosis.

Treatment

Treatment depends on the underlying disorder. The goal is to remineralize the bone safely, without producing hypercalcemia or hypercalciuria, which suggest vitamin D toxicity. Vitamin D is safe when given at appropriate intervals. In patients with osteomalacia caused by vitamin D deficiency, 50,000 or 100,000 IU po once/day for 1 to 2 wk, followed by a maintenance dose of 400 to 800 IU po once/day, is sufficient. If malabsorption occurs, then maintenance doses of 10,000 to 50,000 IU po once/day may be needed. Close monitoring of serum and urine Ca levels is critical.

Because 1,25-dihydroxyvitamin D (calcitriol) is the potent hormonal form of vitamin D, the margin of safety is the smallest. Replacement doses range from 0.25 to 2 µg/day po, and patients should be monitored for hypercalcemia and hypercalciuria. In neoplastic osteomalacia, 1,25-dihydroxyvitamin D and phosphate supplementation may ameliorate the osteomalacia, but this therapy is difficult and may not be completely successful. Every effort should be made to find and remove the tumor.

In hypophosphatemic disorders, including congenital and renal or GI forms and neoplastic osteomalacia, phosphate replacement is critical. However, oral phosphate tends to cause diarrhea. To minimize this effect, K and Na phosphate should be given in divided doses that are increased gradually to bring the phosphate concentration at least into the low-normal range. Elemental phosphorus (250 mg qid) should be given with a full glass of water. In patients with severe or symptomatic hypophosphatemia, the dosage may be increased to as much as 3 g/day po or 2.5 to 5.0 mg/kg in 0.9% saline solution IV. Excessive phosphate therapy or too-rapid repletion may result in hypocalcemia.

All patients with osteomalacia need to maintain adequate intakes of Ca (1000 to 1500 mg/day). In cases of malabsorption, parenteral Ca may be required. Appropriate supportive measures are taken.

This topic was last updated February 2006.