MON-LB71 Adult Hypophosphatasia and Postmenopausal Osteoporosis: A Challenging Case

摘要

Introduction: Hypophosphatasia (HPP) is a rare disease that cause osteomalacia and premature tooth loss due to abnormal bone mineralization. The clinical presentation ranges from severe neonatal and infantile HPP with a high morbidity and mortalilty to mild Adult HPP. The ranging spectrum is possibly due to autosomal recessive versus autosomal dominant missense mutations at the gene that encodes TNSALP. The hallmark of the disease is a low serum total alkaline phosphatase level (ALP). It is important to diagnose adult HPP particularly to refrain from treating with bone antiresorptive medications. Low levels of alkaline phosphatase generally are undectected in the adult population even in patients with osteoporosis and fractures. We describe a case of a woman with postmenopausal osteoporosis without fractures diagnosed with adult HPP. The clinical course and management is described below. Case Description: A 62 y.o. women was referred for evaluation and treatment of osteoporosis. She had no fractures, including during childhood, no history of premature deciduous teeth loss, dental problems or nephrolithiasis. No family history of osteoporosis or fractures. Menopause at age 48 without hormone replacement therapy. Evaluation for secondary causes of osteoporosis was normal including serum TSH, calcium, phosphate, PTH, 24 hours urinary calcium and vitamin D-25. ALP ranged from 33-40 U/L (nl 37-126) before therapy. She was treated with raloxifene for 2 years. Therapy was switched to alendronate due to a decrease in bone density. She subsequently treated with alendronate for 5 years until 5/2012. Due to a decrease in bone density alendronate therapy was reinstituted between Jan 2013-Jan 2016 but in spite of therapy and a CTX level of 333 pg/ml bone density in the spine decreased significantly. In view of the low ALP and decreasing bone density while on bisphosphonate and a high B6 level (B6= 37 nl: -27) a genetic test for HPP and a compound heterozygote mutation in ALPL gene was detected. Her daughter was also found to have low ALP and carries the same mutation. Bone density has been stable since bisphosphonate therapy was stopped (spine T -3.2, LT femoral neck T -2.9) CTX 360 pg/ml. Recently therapy with raloxifene was initiated in view of the low bone density and high risk of fractures. Conclusion: The proper diagnosis and management of patients with adult HPP is challenging because the diagnosis may be missed in patients with borderline low ALP and on the other hand the proper managent of osteoporosis in these patients is not known.