Poster Presentation ESA-SRB-ANZBMS 2024 in conjunction with ENSA
A case report of Romosozumab for treatment of hypophosphatasia with comorbid osteoporosis (#626)
Background
Hypophosphatasia is a rare genetic cause of osteomalacia caused by insufficient tissue non-specific alkaline phosphatase (TNSALP or ALP) (1). Treatment options are limited, as enzyme replacement with Asfotase alfa is not funded for adults, and anti-resorptive agents are contraindicated due to the increased risk of atypical femoral fracture, complicating treatment of comorbid osteoporosis (2).
Case presentation
A 67-year old man was referred with multiple atraumatic metatarsal fractures despite six years of antiresorptive therapy for osteoporosis (alendronate for four years, followed by denosumab for two years). He reported several other features typical of hypophosphatasia, including chronic musculoskeletal pain, premature loss of dentition, and delayed fracture healing. Osteoporosis was diagnosed at age 61 on DEXA scan, with a left femoral neck T-score of -2.9 (see table 1). His only risk factor was chronic steroid treatment for suspected polymyalgia rheumatica (diagnosed for chronic pain despite normal inflammatory markers). Secondary screening demonstrated normal biochemistry, vitamin D, parathyroid hormone and thyroid function. ALP was persistently low, between 12 – 17U/L (reference range 35 – 110 U/L). Following diagnosis of hypophosphatasia, and revision of his polymyalgia rheumatica diagnosis, denosumab was discontinued, prednisolone was weaned and Romosozumab commenced. 12-months later, his metatarsal fractures had healed and he had no incident fractures. His chronic pain and mobility had improved, and ALP had increased to 25 U/L. Impact on bone mineral density was mixed, with improved BMD at the lumbosacral spine, however reduction at the left femoral neck (see table 1).
Conclusion
Hypophosphatasia presents with atypical fractures and low ALP. Limited case reports have shown improved pain and fracture healing following teriparatide in patients with hypophosphatasia (3). We present the second reported case of romosozumab in a patient with hypophosphatasia and osteoporosis, with good clinical response following failure with traditional antiresorptive agents.
- 1. Tournis, S, Yavropoulou, M, Polyzos, S & Doulgeraki, A 2021, ‘Hypophosphatasia’, Journal of Clinical Medicine, vol. 10, no. 23, p. 5676.
- 2. Kim, S-M, Korkmaz, F, Sims, S, Ryu, V, Yuen, T & Zaidi, M 2023, ‘Musculoskeletal and neurocognitive clinical significance of adult hypophosphatasia’, Osteoporosis and sarcopenia, vol. 9, Elsevier BV, no. 4, pp. 115–120.
- 3. Salles Reis, F & Lazaretti-Castro, M 2023, ‘Hypophosphatasia: from birth to adulthood’, Archives of Endocrinology and Metabolism, vol. 67, Brazilian Society of Endocrinology and Metabolism, no. 5.