Circulating RANKL is not a reliable biomarker for bone loss in primary hyperparathyroidism

Grigorie, Daniel; Şucaliuc, Alina; Neacşu, Elena; Militaru, Roxana; Diaconescu, A.; Ivan, Mirela

doi:10.1530/boneabs.1.pp488

Cited by 1 publication

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“…Denosumab is a monoclonal antibody that inhibits osteoclast activity through inhibition of receptor activator of nuclear factor kB ligand (RANKL) that has been approved for treatment of postmenopausal osteoporosis and for the prevention of skeletal-related events We have previously shown that serum RANKL levels are variably increased in patients with primary hyperparathyroidism (PHPT) and correlate with both markers of bone turnover and bone loss; also, serum RANKL/OPG ratio correlated significantly with bone loss at the femoral neck (1). Increased RANKL/ OPG ratio has been reported previously after administration of hPTH (1-34) sc daily (2) and in bone biopsies (transcripts ratio) from patients with primary hyperparathyroidism (3).…”

Section: Introductionmentioning

confidence: 99%

A Single-Dose, Open-Label, Prospective Clinical Study of Denosumab in Patients with Primary Hyperparathyroidism

Grigorie¹

2014

Acta Endo (Buc)

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Background. The purpose of this study was to observe the effects of denosumab on bone mineral density (BMD), bone turnover markers and serum calcium in patients with primary hyperparathyroidism (PHPT) and osteoporosis.Methods. Seven consecutive patients with PHPT were administered a single subcutaneous injection of denosumab, 60 mg. The subjects were followed up to 6 months: serum calcium on days 1,3,7,14,30 and at 3 months and 6 months; serum intact parathyroid hormone (iPTH), C-telopeptide (CTX) and N-mid osteocalcin at baseline, 3 months and 6 months. BMD by DXA, at the femoral neck (FN) and lumbar spine (LS), were measured at baseline and at 6 months.Results. The patients (mean age= 69.8 yrs, range 62-81) had mild PHPT (mean total calcium = 10.8 mg/dL; mean PTH = 148.9 pg/mL); all had osteoporosis and four were currently treated with various bisphosphonates (BP). After 6 months mean LS BMD increased significantly by 4.5 % (p = 0.04) and mean FN BMD by 2.4% (p= 0.09 two-tailed; p = 0.047 one-tailed). Serum CTX decreased significantly by 90% at 3 months (p = 0.04), and by 48% at 6 months (p = 0.02); the similar changes for serum osteocalcin were 41% and 42% (p = 0.07, one-tailed), respectively. In the first two weeks, serum total Ca variably decreased vs. baseline (0.5 to 2.8 mg/dL) in six out of seven patients. After 6 months mean total serum Ca nonsignificantly increased vs. baseline (11.4 mg/dL vs. 10.8 mg/dL, p = 0.1). Serum iPTH levels did not significantly change at both 3 and 6 months; after 6 months there was a trend toward decreased values (p = 0.03 onetailed).Conclusion. Denosumab increased BMD at both lumbar spine and femoral neck, and significantly decreased bone resorption in patients with PHPT. The effects on hypercalcemia were mild and transient, with a numerical increase after 6 months.

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Section: Introductionmentioning

confidence: 99%

A Single-Dose, Open-Label, Prospective Clinical Study of Denosumab in Patients with Primary Hyperparathyroidism

Grigorie¹

2014

Acta Endo (Buc)

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show abstract

Circulating RANKL is not a reliable biomarker for bone loss in primary hyperparathyroidism

Cited by 1 publication

References 15 publications

A Single-Dose, Open-Label, Prospective Clinical Study of Denosumab in Patients with Primary Hyperparathyroidism

A Single-Dose, Open-Label, Prospective Clinical Study of Denosumab in Patients with Primary Hyperparathyroidism

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