Time to onset of efficacy in fracture reduction with current anti-osteoporosis treatments

Abstract

Early prevention of future fracture is an important goal in those at risk. A similar 3-year fracture efficacy is reported for most osteoporosis agents. Onset of fracture efficacy may be useful to help tailor treatment based on risk. We reviewed the peer-reviewed literature for onset of fracture efficacy data on the commonly prescribed osteoporosis treatments. All papers were reviewed independently by at least two reviewers for onset of efficacy for morphometric vertebral fracture (MVF), clinical vertebral fracture (CVF), nonvertebral fracture (NVF), hip fracture, and any clinical fracture (ACF). Alendronate is reported to reduce multiple CVF by 6 months; all CVF, NVF, and multiple ACF by 12 months; and all ACF and hip fracture by 18 months. Ibandronate is reported to reduce MVF by 12 months and NVF by 36 months. Raloxifene is reported to reduce CVF by 3-6 months and NVF by 36 months. Risedronate is reported to reduce CVF and NVF by 6 months, and hip fracture by 12 months. Strontium ranelate is reported to reduce MVF, CVF, NVF, and ACF by 12 months, and hip fracture by 36 months. Zoledronic acid is reported to reduce MVF, CVF, and ACF by 12 months, NVF by 24 months, and hip fracture by 36 months. Although direct comparisons are limited, based on the available literature, risedronate, followed by alendronate, have the earliest onset of benefit across the range of fracture types. Onset of efficacy may be an important consideration in the selection of treatment for some patients.

Models of care for the delivery of secondary fracture prevention after hip fracture: a health service cost, clinical outcomes and cost-effectiveness study within a region of England

“…Compounding this issue is that the earliest demonstrated time to antiosteoporosis treatment efficacy in terms of hip fracture risk reduction is 6-36 months. 126 Specifically, zoledronic acid has been shown to reduce clinical fracture risk after hip fracture only after 12 months. 119 In the present analysis, 35% and 63% of second hip fractures within 2 years occurred within the first 6 and 12 months, respectively.…”

Examining the treatment gap and risk of subsequent fractures among females with a fragility fracture in the US Medicare population

“…Our study has a shorter follow-up period compared to RCT and other RWE studies; therefore, the impact may be greater with a longer follow-up. Additionally, a systematic review of RCTs demonstrated the impact of osteoporosis medication on time to fracture reduction, ranging from 6-36 months of treatment [37]. Our RWE study results among Medicare women can be tied to the fact that osteoporosis treatments show an increased effectiveness against subsequent fractures and support the efficacy demonstrated through RCTs in the past.…”

Interaction Between Bone and Muscle in Older Persons with Mobility Limitations

“…Although few data are available in older groups [321], there is acceptable evidence to recommend the BPs, strontium ranelate, or teriparatide for vertebral fracture relative risk reduction (RRR) in persons aged > 75 years [311, 322]. A significant RRR of vertebral fracture at 1 year has been demonstrated for risedronate (RRR 81%; p<0.001), teriparatide (RRR 65%; p<0.05) and strontium ranelate (RRR 59%; p=0.002), and at 3 years for risedronate (RRR 44%; p=0.003), alendronate (RRR 38%; p<0.05), strontium ranelate (RR 32%; p=0.013) and denosumab in high risk fracture women (16.6% placebo vs. 7.5% denosumab; p< 0.001) [322].…”

“…Concerning the non-vertebral fractures, there is evidence for protective effects of strontium ranelate after 1 and 3 years of treatment (RRR 41%; p=0.027 and RRR 31%; p=0.011) [311], for denosumab (HR 0.80; p=0.01) [321] and zoledronic acid (HR 0.73, p=0.002) after three years with efficacy almost superimposed to those of younger persons [325]. Risedronate demonstrated to reduce non-vertebral fracture only in a combined analysis of subjects participating in the HIP study (70–79 years and ≥80 years groups) [323].…”

“…The studies that specifically investigated hip fracture prevention as the primary outcome — the HIP study [326], the Clodronate Study [322, 324] and the FREEDOM Study (Denosumab: post-hoc analysis and 2-year extension) [321, 323, 325], suggest a weak efficacy after 3 years of treatment. Hip fracture reduction was demonstrated for risedronate in a subgroup analysis including women with osteoporosis (those 70 to 79 years old), where the incidence of hip fracture among those assigned to risedronate was 1.9%, as compared with 3.2% among those assigned to placebo (RRR 0.6; p=0.009).…”