Denosumab versus zoledronic acid in patients previously treated with zoledronic acid

Abstract

In patients previously treated with zoledronic acid, denosumab reduces bone turnover more than zoledronic acid, but the increases in LS BMD are comparable. Furthermore, denosumab administration results in reversible inhibition of the metabolically significant endogenous free soluble RANKL levels. Serum sclerostin is not affected by either agent.

Zoledronate for the Prevention of Bone Loss in Women Discontinuing Denosumab Treatment. A Prospective 2-Year Clinical Trial

“…Earlier studies of similar design in bisphosphonate‐treated women with postmenopausal osteoporosis reported increases in BMD after 12 months with both agents. Dmab induced generally greater increases than ZOL the magnitude of which might depend on the length and type of bisphosphonate pretreatment . Our results in Dmab‐treated women are similar to those of bisphosphonate‐treated women in showing larger increases in LS‐BMD with Dmab compared with ZOL which were not, however, statistically significant.…”

Novel therapies for osteoporosis

“…Corroborating the above, A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT 9 9 in women previously treated with oral bisphosphonates, denosumab was superior to alendronate [16], risedronate [18], and ibandronate [17] in terms of BMD accrual and BTM suppression, while a direct comparison with zoledronic acid is ongoing (NCT01732770). By contrast, in patients previously treated with zoledronic acid, denosumab achieved similar increases with zoledronic acid in LS BMD despite the more prominent reduction of BTM [33]. Notably, all the above comparisons refer to BMD changes and do not provide adequate information concerning comparative fracture reduction, as the number of patients in those studies was too small to permit such an analysis.…”

Advances in Controlled Drug Delivery for Treatment of Osteoporosis

“…The antibody inhibits RANKL, a potent mediator of osteoclast development and activity [32]. RANK has a much greater specificity for binding to the RANKL cell surface molecule than its natural competitor, OPG, which is secreted by bone marrow and a number of other cell types [33]. Denosumab promoted a higher BMD in the lumbar spine and hip and reduction in bone turnover markers than did alendronate, risendronate, ibandronate, zolendronate, raloxifene, and calcitonin throughout an exploratory three year study [34].…”

“…PTH is known to exhibit resorptive properties in combination with vitamin D, which is important for regulating serum calcium and phosphate levels in the body. When intermittently administered, PTH(1–34) demonstrates bone stimulating properties [33, 41]. The complete hormone sequence, rhPTH(1–84), demonstrates increased anabolic effects in bone marrow cells in vitro [42].…”

“…The complete hormone sequence, rhPTH(1–84), demonstrates increased anabolic effects in bone marrow cells in vitro [42]. Under normal to slightly elevated serum calcium levels, activation of PTH-receptors results in phospholipase C-stimulated production of inositol triphosphate and diacylglycerol, with subsequent intracellular calcium mobilization combined with protein kinase C activation [33]. These pathways activated by PTH subsequently affect lipoprotein receptor-related protein-5 or 6 (LRP5/6) mediated canonical wingless (Wnt) signaling, which promotes osteoblast development by downregulating sclerostin and RANKL expression.…”