MON-741 - Treatment of Adult-Onset Hypophosphatasia with Anabolic Therapy

INTRODUCTION
Hypophosphatasia (HPP) is a rare disorder characterized by loss-of-function in ALPL gene responsible for encoding Tissue-nonspecific alkaline phosphatase (TNALP) with a prevalence of 1:300,000 and 1:500(1). TNALP is important for skeletal matrix mineralization, and its deficiency can lead to premature loss of deciduous teeth, abnormalities in mineral homeostasis and impaired vitamin B6 metabolism leading to decreased synthesis of neurotransmitters.

CASE PRESENTATION
65-year-old man with a history of ankylosing spondylitis, hyperlipidemia, chronic compression fracture of C7 was referred for evaluation of severe osteoporosis (T-score of -3.7 to -4) being treated with alendronate. Laboratory workup revealed consistently low alkaline phosphatase (11 U/L, normal 40 - 150), bone specific ALP (1.9 mcg/L, normal 7.6 - 14.9), elevated vitamin B6, and vitamin D. Serum levels of Parathyroid Hormone, calcium, phosphorus, magnesium, cortisol, and TSH were within normal limits. On physical exam, he was found to be thin and of short stature. He had a 20-year history of back, neck and shoulder pain, difficulty gaining weight, and premature loss of teeth by age 45 and denied prior history of fractures. Patient declined genetic testing that was discussed for initiation of asfotase alfa and was then started on off-label use of abaloparatide, briefly transitioned to teriparatide due to medication availability, before resuming abaloparatide. After a year of treatment, there was an improvement in bone marrow density with an improvement in lumbar spine (+11.6%, non-diagnostic due to history of ankylosing spondylitis) and left hip (+4.5%), improvement in hip pain and increased level of ALP.

CONCLUSION
This case highlights the importance of keeping a broad differential diagnosis when approaching bone disorders. Misdiagnosis of hypophosphatasia as osteoporosis can lead to the initiation of pharmacological therapy that is contraindicated. Asfotase alfa, the only approved pharmacological treatment for HPP, is expensive and may not be attainable to patients. Teriparatide and abaloparatide have been reported to improve symptoms, quality of life, biochemical markers of bone remodeling, fracture repair, and increased skeletal mineralization(5-7). Similarly, to previous cases reported the initiation of these medications led to biochemical and symptomatic improvement with increased skeletal mineralization. This case highlights the importance of considering alternative diagnoses in adults presenting with osteoporosis and decreased alkaline phosphatase. Additionally, we describe the use of anabolic agents such as teriparatide and abaloparatide in patients when treatment with asfotase alfa is unavailable or inaccessible to patients.

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