Denosumab or Zoledronic Acid in Postmenopausal Women With Osteoporosis Previously Treated With Oral Bisphosphonates

Abstract

Context:Denosumab and zoledronic acid (ZOL) are parenteral treatments for patients with osteoporosis.Objective:The objective of the study was to compare the effect of transitioning from oral bisphosphonates to denosumab or ZOL on bone mineral density (BMD) and bone turnover.Design and Setting:This was an international, multicenter, randomized, double-blind trial.Participants:A total of 643 postmenopausal women with osteoporosis previously treated with oral bisphosphonates participated in the study.Interventions:Subjects were randomized 1:1 to sc denosumab 60 mg every 6 months plus iv placebo once or ZOL 5 mg iv once plus sc placebo every 6 months for 12 months.Main Outcome Measures:Changes in BMD and bone turnover markers were measured.Results:BMD change from baseline at month 12 was significantly greater with denosumab compared with ZOL at the lumbar spine (primary end point; 3.2% vs 1.1%; P < .0001), total hip (1.9% vs 0.6%; P < .0001), femoral neck (1.2% vs −0.1%; P < .0001), and one-third radius (0.6% vs 0.0%; P < .05). The median decrease from baseline was greater with denosumab than ZOL for serum C-telopeptide of type 1 collagen at all time points after day 10 and for serum procollagen type 1 N-terminal propeptide at month 1 and at all time points after month 3 (all P < .05). Median percentage changes from baseline in serum intact PTH were significantly greater at months 3 and 9 with denosumab compared with ZOL (all P < .05). Adverse events were similar between groups. Three events consistent with the definition of atypical femoral fracture were observed (two denosumab and one ZOL).Conclusions:In postmenopausal women with osteoporosis previously treated with oral bisphosphonates, denosumab was associated with greater BMD increases at all measured skeletal sites and greater inhibition of bone remodeling compared with ZOL.

DIAGNOSIS OF ENDOCRINE DISEASE: Bone turnover markers: are they clinically useful?

“…In the FREEDOM Study, there was no overlap in CTX levels between treated and control subjects at one month indicating that everyone appears to respond (29). Denosumab results in a greater inhibition of bone resorption than zoledronic acid (30). PINP decreases over several months to a lesser extent than the bone resorption markers and remains suppressed with continued dosing for up to 8 years (31).…”

Osteoporosis: a discussion on the past 5 years

“…Its current indications include postmenopausal women with osteoporosis, women receiving aromatase inhibitor therapy (prevents the conversion of androgens to estrogens) for breast cancer treatment with an increased fracture risk, men with osteoporosis and men at high risk for fracture who receive androgen-deprivation therapy for nonmetastatic prostate cancer [20]. A recent trial showed a significant reduction in vertebral and non-vertebral fractures and denosumab was as effective as zolendronate [77,78]. It is a biannual injection, making patient compliance easier as well.…”

Marine Natural Products: New Avenue in Treatment of Osteoporosis

“…Besides this, Teriparatide in combination with Denosumab enhanced BMD to a greater extent than either drug alone (Tsai et al, 2013). Research proves that postmenopausal women having low bone mass can be treated more effectively with Denosumab than with oral bisphosphonates (Miller et al, 2016;McClung, 2017).…”