MON-495 Hypophosphatasia: A Rare Cause of Osteoporosis in a Young Adult Male

Abstract

Introduction: Secondary osteoporosis is due to an identifiable cause of osteoporosis. Hypophosphatasia is a rare cause of secondary osteoporosis and needs to be considered when evaluating osteoporosis in young people. We present a case of secondary osteoporosis initially thought to be a result of malabsorptive disorder and chronic steroid use, with eventual diagnosis of autosomal dominant hypophosphatasia as the primary underlying cause. Clinical Case: A 24 year old male who was seen for evaluation of osteoporosis. He reported an extensive history of fractures about 26 in total, including wrist, shoulders, nose, and metatarsals. Past history was also significant for bowed legs at birth requiring osteotomies and spontaneous loss of several teeth with root intact, requiring extractions. He was also diagnosed with Crohn’s disease at 17 years old and history of steroid use, however was not on steroids at time of initial evaluation. He was diagnosed with bilateral avascular necrosis at age 18 years and needed bilateral hip replacement at age 20 years. There was no family history of skeletal disorders. DEXA scan obtained for the assessment of bone density revealed a Z score of -2.6 in the lumbar spine and -2.1 in the distal forearm. Further evaluation for secondary causes of osteoporosis revealed a normal TSH, PTH, tryptase, vitamin D and testosterone levels. Bone turnover markers were normal except for a low alkaline phosphatase. It was noted that the patient had a persistently low alkaline phosphatase for the last 6 years despite his frequent fractures. Hypophosphatasia was suspected given the history and the low alkaline phosphatase levels. Pyridoxal 5-phosphate was elevated at 77mcg/L (normal 5-50mcg/L). Genetics evaluation revealed a heterozygous, missense mutation in ALPL gene, confirming diagnosis of autosomal dominant hypophosphatasia. He was started on enzyme replacement therapy with asfotase alpha. Conclusion: Hypophosphatasia is a rare metabolic bone disease due to a deficiency of alkaline phosphatase which may present from infancy to adulthood. Diagnosis is made by finding a low alkaline phosphatase level and elevated 5 pyridoxal phosphate. Enzyme replacement therapy with asfotase alpha is the mainstay of treatment. It is probably underdiagnosed secondary to its rarity and therefore must be considered in any young patient who presents with osteoporosis.