Treatment of osteoporotic fractures in alkaptonuria by teriparatide stimulates bone formation and decreases fracture rate – A report of two cases

Abstract

Two cases of advanced alkaptonuria (AKU) with co-existing osteoporosis are described. Case 1 developed multiple non-vertebral fragility fractures, while Case 2 developed vertebral fragility fractures, both refractory to bisphosphonates. Difficulties in diagnosing osteoporosis in AKU complicated by extensive calcifying and ossifying spondylosis are discussed. Both patients continued to fracture despite nitisinone therapy for metabolic control of AKU, as well as bisphosphonate antiresorptive therapy for osteoporosis. Subsequently the patients were treated with teriparatide 20 μg subcutaneous injections daily for two years, leading to reduction in fractures soon after commencing therapy in both cases. Markers of bone remodelling P1NP and CTX were stimulated. No complications due hypercalcaemia or calcification were encountered in either case. We conclude that teriparatide is an effective adjunct in the treatment of AKU when bisphosphonates prove ineffective.

Dilemmas in the diagnosis and management of osteoporosis in a patient with alkaptonuria: Successful treatment with teriparatide

“…After 5 years of treatment with bisphosphonates, our patient was treated with teriparatide. More recently, Ranganath et al in 2021 have also demonstrated the effectiveness of teriparatide in 2 AKU patients 6 . Thus, our patient represents the third AKU patient with bisphosphonate‐resistant osteoporosis who was treated successfully with teriparatide.…”

“…More recently, Ranganath et al in 2021 have also demonstrated the effectiveness of teriparatide in 2 AKU patients. 6 Thus, our patient represents the third AKU patient with bisphosphonate‐resistant osteoporosis who was treated successfully with teriparatide. The anabolic actions of PTH occur because of its direct effects on cells of the osteoblast lineage and indirect effects through the induction of IGF‐I (insulin‐like growth factor‐1) and the suppression of sclerostin with the consequent enhancement of Wnt signaling and by suppressing Notch signaling.…”

“…Ranganath et al 6 reported that DXA (dual‐energy X‐ray absorptiometry) scan is not reliable in AKU patients due to extensive calcification of intervertebral discs as well as the extensive degenerative arthritis or joint replacements. In our patient, although an initial and serial DXA scans showed normal BMD at the lumbar spine, the BMD was likely falsely elevated; however, her hip BMD done at the age of 61 years showed osteoporosis (femoral neck T‐score −2.9).…”

“… 1 , 2 , 3 , 4 , 5 Ranganath et al recently reported successful treatment of osteoporosis with teriparatide in 2 patients with AKU. 6 We report the first case of long‐term follow‐up of a 69‐year‐old woman who developed fragility fractures despite receiving bisphosphonate therapy and was successfully treated with teriparatide.…”

Alkaptonuria with Fracture Neck of Femur – A Case Report

“…There are a good number of publications on alkaptonuria presenting with arthritis but there are only a handful of case reports in the context of fractures. Ranganath et al [ 5 ] described two cases of advanced alkaptonuria with coexisting osteoporosis. One patient developed multiple non-vertebral fragility fractures and the other patient developed vertebral fragility fractures while on nitisinone therapy and bisphosphonates therapy.…”