Comparison of bone histomorphometry in hypophosphatemia and vitamin D deficiency osteomalacia
Bhan A, Kulkarni P, Honasoge M, Palnitkar S, Qiu SJ, and Rao DS. Comparison of bone histomorphometry in hypophosphatemia and vitamin D deficiency osteomalacia. Endocrine Reviews 2017; 38(3)
Background:Osteomalacia (OM) can be caused by several conditions, but the two most common causes are phosphate and vitamin D deficiency (1). Although calcium deficiency rickets and OM have been reported in children, OM due to calcium deficiency has not been reported in adults. We had the unique opportunity to compare the severity of mineralization defect in the two most common causes of OM. Methods: We examined the invivo double tetracycline labelled bone histomorphometric findings in 24 patients with vitamin D deficiency (21 patients with malabsorption and 3 with nutritional vitamin D deficiency) and 7 patients with hypophosphatemia (4 patients with tumor and 3 with tenofovir induced). Since there were no differences in bone histomorphometric findings between the two groups of either variety we combined the respective groups for analyzing the difference between vitamin D deficiency and hypophosphatemic OM. As expected, patients with vitamin D deficiency had very low or undetectable serum 25-hydroxyvitamin D (5.4±3.8ng/ml) and high PTH (277±90pg/ml) levels, whereas both were normal in hypophosphatemic patients (26.5±5.4ng/ml and 46.6±13.5pg/ml; p<0.001 for the difference for both) . Mean serum phosphate level, by definition, was very low in the hypophosphatemic patients, but significantly lower than in the vitamin D deficient patient (1.6 ±0.4mg/dl Vs. 2.9±0.5mg/dl; p<0.001) Results: For the entire group, osteoid indices (surface, width & volume) were high, none had double tetracycline labels and all had severe mineralization defect (mineral apposition rate =0) confirming OM in each patient. However, osteoid volume, an index of the severity of OM, was significantly higher in hypophosphatemic compared to vitamin D deficient patients (33.6 Vs. 21.7% of the bone surface; p=0.049) indicating a more severe mineralization defect in hypophosphatemic OM. In contrast resorption surface, an index of PTH effect on bone, was significantly higher (4.52 Vs. 1.42% of non-osteoid surface; p=0.009) in vitamin D deficiency compared to phosphate deficiency. Finally, cortical thickness was lower in vitamin D deficiency than in phosphate deficiency, but did not reach statistical significance (0.51 Vs. 0.94mm; p=ns), most likely due to the small sample size of hypophosphatemic OM patients. Collectively, the data suggest a more severe mineralization defect in phosphate than in vitamin D deficiency OM. Conclusions: Mineralization defect is more severe in hypophosphatemic OM. Cortical thinning, a characteristic feature of excess PTH, is seen only in vitamin D deficiency, consistent with our previous findings (2,3). To the best of our knowledge this is the first such compartive study of its kind.