Reduced bone mineral density and low parathyroid hormone levels in patients with the adult form of hypophosphatasia

Summary Hypophosphatasia is a heritable metabolic bone disease with characteristically reduced levels of alkaline phosphatase (ALP) in the blood, liver, kidney and bone. ALP levels are normal in the intestine and placenta. About 300 patients have been reported so far in the literature. Three kindreds with 52 known subjects are described here, whereby 12 subjects could be examined osteologically. Four subjects were patients and had clinical signs of the disease: spontaneous fractures of the metatarsals or femora and low ALP serum levels ranging between 8 and 23 U/1 (normal range 40–170 U/1). Four other members without fractures had reduced ALP levels; they might be carriers of the disease and develop symptoms later in life. The four remaining subjects had normal ALP levels and no signs of the disease. Serum levels of intact parathyroid hormone (iPTH) were found to be in the lower normal range and serum calcium levels in the upper normal range. There was a significant (P<0.05) negative correlation between iPTH and serum calcium levels (r=–0.78). Urinary calcium excretion was increased in 3 subjects with fractures. 25-OH-D₃ levels were increased in 6 of 8 subjects without any treatment. The bone mineral density (BMD) was measured using dual X-ray absorptiometry of the lumbar spine, representing mainly trabecular bone, and single-photon absorptiometry of the forearm, measuring mainly cortical bone. Z-scores of the spinal bone mass ranged between 0.38 and –1.95 SD; Z-scores of the forearm bone mass ranged between 0.53 and –2.47 SD with the lowest values in patients with fractures. There was a significant (P<0.05) correlation between serum ALP levels and forearm BMD (r=0.83). We conclude from these data that patients with the adult form of hypophosphatasia have decreased forearm and subnormal spinal bone mass, as well as reduced serum levels of iPTH.Abbreviations BMD bone mineral density - ALP alkaline phosphatase - iPTH intact parathyroid hormone - 25-OHD₃ 25-hydroxyvitamin D₃ - SD standard deviation - PEA phosphoethanolamine - PPi inorganic pyrophosphate - PLP pyridoxal-5-phosphate - cDNA clonal desoxyribonucleic acid - U/S Ca²⁺ urinary/serum calcium - DXA dual X-ray absorptiometry - DPA dual photon absorptiometry - SPAD bone density of distal forearm measured by single photon absorptiometry - SPAP bone density of proximal forearm measured by single photon absorptiometry