THERAPY OF ENDOCRINE DISEASE: Denosumab vs bisphosphonates for the treatment of postmenopausal osteoporosis

Abstract

The most widely used medications for the treatment of osteoporosis are currently bisphosphonates (BPs) and denosumab (Dmab). Both are antiresorptives, thus targeting the osteoclast and inhibiting bone resorption. Dmab achieves greater suppression of bone turnover and greater increases of bone mineral density (BMD) at all skeletal sites, both in naïve and pretreated patients. No superiority on fracture risk reduction has been documented so far. In long-term administration, BPs reach a plateau in BMD response after 2-3 years, especially at the hip, while BMD increases progressively for as long as Dmab is administered. Both BPs and Dmab are generally considered safe, although they have been correlated to rare adverse events, such as osteonecrosis of the jaw and atypical femoral fractures. Dmab should be preferred in patients with impaired renal function. BPs are embedded in the bone, from which they are slowly released during bone remodeling, therefore continuing to act for years after their discontinuation. In contrast, Dmab discontinuation fully and rapidly reverses its effects on bone markers and BMD and increases the risk for fractures; therefore, Dmab discontinuation should be discouraged, especially in previously treatment-naïve patients, regardless of the conventional fracture risk. In case of discontinuation, other treatment, mainly BPs, should immediately follow, although the optimal sequential treatment strategy is yet to be defined. Combination of teriparatide with Dmab or zoledronic acid, but not alendronate, provides increased BMD gains at all sites. In conclusion, both BPs and Dmab are safe and efficient therapeutic options although their particularities should be carefully considered in an individual basis.

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

“…Dmab induced generally greater increases than ZOL the magnitude of which might depend on the length and type of bisphosphonate pretreatment. (33)(34)(35) Our results in Dmabtreated 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.…”

“…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.…”

The effect of previous treatment with bisphosphonate and renal impairment on the response to denosumab in osteoporosis: a ‘real-life’ study

“…BPs are indeed contra-indicated in patients with chronic kidney disease (CKD), particularly those with GFR < 35 ml/ min (in the case of alendronate) or < 30 ml/min (in the case of risedronate). Denosumab, however, can be used in patients who have osteoporosis and CKD, although there is an increased risk of hypocalcaemia in patients with severe renal impairment or end-stage renal disease [5][6][7]. Post hoc analysis of data from the FREEDOM trial showed that denosumab was still effective in terms of fracture reduction and improvement in BMD in patients with CKD stage 3 and 4 [8].…”

Differential protective effects of bisphosphonates and denosumab on primary breast cancer risk, potentially to be modified by statins: a retrospective study using electronic health records

“…Denosumab is a newer monoclonal antibody rst approved by FDA for treatment of postmenopausal osteoporosis in June 2010. It suppresses bone resorption by binding to receptor activator of nuclear factor kappa-B ligand (RANKL), preventing it from binding to its receptor on cell surfaces of not only osteoclasts but also osteoclasts precursors and decreasing osteoclast formation, activity, and survival [4,5].…”

“…The anti-osteoporotic effects of bisphosphonates and denosumab are different: denosumab is more effective and faster in improving bone mass density; but effects of bisphosphonates continue for years after drug discontinuation because they are imbedded in the bone while denosumab discontinuation fully and rapidly reverse its effects on bone markers and bone mineral density [4][5][6]. Denosumab is contraindicated in severe infection, but is preferred in patients with renal failure.…”