Treatment with zoledronic acid subsequent to odanacatib prevents bone loss in postmenopausal women with osteoporosis.

Treatment with zoledronic acid 5 mg maintained bone turnover markers in the premenopausal range, increased lumbar spine bone mineral density, and maintained hip bone mineral density in women previously treated with odanacatib 50 mg weekly. INTRODUCTION: The development of odanacatib (ODN), a cathepsin K inhibitor, for treatment of osteoporosis was discontinued due to an increased risk of cardiovascular events. As the treatment is considered reversible, participants from the LOFT trial in Aarhus, Denmark, were offered treatment with zoledronic acid (ZOL). METHODS: Sixty-seven postmenopausal women were treated with ZOL 5 mg and followed for 12 months. Of these, 39 had received ODN for 7 years and 28 had received placebo for 5 years and ODN for 2 years. Bone turnover markers (BTM) were measured 3, 6, and 12 months after ZOL, and DXA of spine and hip were performed at time of ZOL treatment and after 12 months. RESULTS: Within the entire study population, BMD at the lumbar spine increased by 2.8 ± 0.9% (mean ± SEM) (p < 0.01) from baseline to month 12. There was no significant change in BMD at the total hip (p = 0.17) or femoral neck (p = 0.39). There was no difference in the changes in BMD from baseline to 12 months between the two groups at any site (p ≥ 0.20 for all). CTX increased by 107 ± 9% (p < 0.001), PINP by 102 ± 16% (p < 0.001), osteocalcin by 32 ± 6% (p = 0.001) and BSAP by 79 ± 37% (p = 0.001) between 3 and 12 months after ZOL. At month 12, BTM were still within the premenopausal reference range. S-25-hydroxyvitamin D increased (p = 0.059), while PTH (p = 0.007) and eGFR (p = 0.014) decreased during the year following ZOL administration. CONCLUSION: Treatment with ZOL 5 mg maintained BTMs in the premenopausal range and prevented bone loss in women previously treated with ODN.

Hypercalcemia after discontinuation of long-term denosumab treatment.

UNLABELLED: Denosumab is used for treatment of osteoporosis. We present a case report of hypoparathyroid hypercalcemia and increased bone turnover associated with discontinuation of treatment for 10 years with denosumab. There is a need for evidence-based guidelines on discontinuation of long-term denosumab treatment to avoid side effects and preserving anti-fracture efficacy. PURPOSE: Denosumab is commonly used as an anti-resorptive agent for the treatment of osteoporosis. After discontinuation of denosumab, however, bone resorption increases again, and the bone mass gained during therapy is rapidly declining. Thus, treatment with denosumab is considered to be reversible. METHODS: We present a case report of asymptomatic hypoparathyroid hypercalcemia in a patient who discontinued long-term treatment with denosumab. RESULTS: A 67-year-old woman with osteoporosis was treated with denosumab 60 mg subcutaneously every 6 months from 2004 to 2014. She received the last injection in May 2014. Routine biochemistry in November 2014 showed increased s-ionized calcium (I-Ca) 1.64 mmol/L (1.18-1.32 mmol/L) and suppressed p-parathyroid hormone (PTH) 1.6 pmol/L (1.6-6.9 pmol/L). The patient was extensively examined, but no underlying disease was found. In January 2015, the patient began treatment with alendronat 70 mg weekly. In April 2015, serum levels of type 1 collagen C-terminal cross-linked telopeptide, procollagen type 1 N-terminal propeptide and bone-specific alkaline phosphatase were still markedly elevated. From then on, I-Ca and PTH normalized and the bone turnover markers (BTM) decreased. CONCLUSION: In this case report, we describe increased BTMs and hypercalcemia associated with discontinuation of 10 years treatment with denosumab. The increase in BTMs is assumed to be temporary and normalization is expected. Since denosumab is commonly used, there is an urgent need for evidence-based guidelines on discontinuation of long-term treatment, avoiding side effects and preserving anti-fracture efficacy.