Endocrine Abstracts

Context: ß-CTX are considered useful markers of response to denosumab and other anti-resorbtive treatments for osteoporosis. We report an unusual case of a completely absent effect of both denosumab and bisphosphonates on bone resorption markers.

Case description: In 2017 a 74-year-old woman sought medical attention at the Endocrinology Unit of Policlinico di Sant’Orsola for the evaluation of an adrenal adenoma associated with osteoporosis. Menopause age was 49. The 2-cm lipid-rich left adrenal adenoma had been incidentally discovered in 2008 and was morphologically stable. BMI was 30.0 kg/m². No signs of hypercortisolism were detected. A densitometry (DXA) scan performed in 2014 showed a femoral neck T-score of −2.3, total hip T-score of −1.1, spine T-score of −3.1. A 1-mg dexamethasone test detected subclinical hypercortisolism (1-mg post-desamethasone cortisol=102 nmol/l). Renal function and 25-OH vitamin D levels were normal. High bone resorption markers were registered (ß-CTX=1.097 ng/ml) while hyperparathyroidism was excluded. A DXA scan was repeated in May 2017 and a worsening of spine BMD (T-score: −3.9) was detected, whereas hip BMD was stable (neck T-score of −2.3, total T-score of −1.2). Three vertebral fractures were diagnosed on a morphometric X-ray of the spine. Denosumab 60 mg was started in May 2017. Six months later, bone resorption markers were elevated (ß-CTX=1.533 ng/ml). Denosumab was continued and ß-CTX retested three months later, which again were confirmed inappropriately high (0.987 ng/ml). Six months after the 2^ndadministration no change occurred (ß-CTX=1.305 ng/ml). A Technetium-99 m Bone Scintigraphy was carried out in March 2018 to exclude primary or secondary bone disease, with no pathological findings, except for signs of osteoarthritis. Denosumab was then stopped and the patient switched to alendronate 70 mg weekly. Six months later, ß-CTX were still elevated (1.408 ng/ml), thus alendronate was stopped. Zoledronate 5 mg was administered intravenously. After one month, ß-CTX were unchanged (1.270 ng/ml). A DXA scan was repeated before the administration of zoledronate, in January 2019, and a bone mineral density (BMD) gain at the spine (T-score: −3.4) was observed, whereas hip BMD remained unaltered (neck T-score of −2.3, total T-score of −1.1). Other secondary causes of osteoporosis were excluded, including mastocytosis.

Conclusion: This is the first ever-described case of a failed response of bone resorption markers to denosumab. Despite high ß-CTX, spine BMD improved. Whether mild and long-standing hypercortisolism may explain a missed response of ß-CTX should be assessed by appropriate studies.