Romosozumab improves lumbar spine bone mass and bone strength parameters relative to alendronate in postmenopausal women: results from the Active-Controlled Fracture Study in Postmenopausal Women With Osteoporosis at High Risk (ARCH) trial

Brown, Jacques P.; Engelke, Klaus; Keaveny, Tony M.; Chines, Arkadi; Chapurlat, Roland; Foldes, A. Joseph; Nogués, Xavier; Civitelli, Roberto; Villiers, T de; Massari, Fabio; Zerbini, Cristiano A. F.; Wang, Zhenxun; Oates, Mary; Recknor, Christopher; Libanati, Cesar

doi:10.1002/jbmr.4409

Cited by 45 publications

(24 citation statements)

References 42 publications

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“…In the primary Phase 2 study, with romosozumab as initial therapy, quantitative computed tomography (QCT) assessments indicated that volumetric BMD and bone strength at the total hip increased 4.1% and 3.6%, respectively, and these changes were a reflection of increments in both cortical and cancellous compartments; similarly, volumetric BMD and bone strength at the lumbar spine increased 17.7% and 27.3%, respectively, with romosozumab, again with demonstrable increments in both cortical and cancellous compartments [ 38 , 39 ]. In a subset of women from ARCH, QCT assessments of the lumbar spine also demonstrated increments in volumetric BMD and bone strength of both cortical and cancellous bone compartments [ 40 ]; however, there is no information about the cortical and cancellous bone compartments at the total hip since QCT assessments were not performed in the hip region in ARCH. In STRUCTURE, with romosozumab after alendronate, volumetric BMD and bone strength at the total hip increased 3.4% and 2.5%, respectively, with improvements in both cortical and cancellous bone compartments; however, gains in both compartments were diminished with the alendronate-to-romosozumab sequence, compared with the romosozumab first sequence [ 12 ].…”

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confidence: 99%

Romosozumab and antiresorptive treatment: the importance of treatment sequence

et al. 2022

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To evaluate whether treatment sequence affects romosozumab response, this analysis reviewed studies where romosozumab was administered before or following an antiresorptive (alendronate or denosumab). Initial treatment with romosozumab followed by an antiresorptive resulted in larger increases in bone mineral density of both hip and spine compared with the reverse sequence. Introduction Teriparatide followed by an antiresorptive increases bone mineral density (BMD) more than using an antiresorptive first. To evaluate whether treatment sequence affects romosozumab response, we reviewed randomized clinical trials where romosozumab was administered before (ARCH, FRAME) or following (STRU CTU RE, Phase 2 extension) an antiresorptive (alendronate or denosumab, respectively). Methods We evaluated BMD percentage change for total hip (TH) and lumbar spine (LS) and response rates (BMD gains ≥ 3% and ≥ 6%) at years 1 and 2 (except STRU CTU RE with only 1-year data available). Results With 1-year romosozumab initial therapy in ARCH and FRAME, TH BMD increased 6.2% and 6.0%, and LS BMD increased 13.7% and 13.1%, respectively. When romosozumab was administered for 1 year after alendronate (STRU CTU RE) or denosumab (Phase 2 extension), TH BMD increased 2.9% and 0.9%, respectively, and LS BMD increased 9.8% and 5.3%, respectively. Over 2 years, TH and LS BMD increased 7.1% and 15.2% with romosozumab/alendronate, 8.5% and 16.6% with romosozumab/denosumab, and 3.8% and 11.5% with denosumab/romosozumab, respectively. A greater proportion of patients achieved BMD gains ≥ 6% when romosozumab was used first, particularly for TH, versus the reverse sequence (69% after romosozumab/denosumab; 15% after denosumab/romosozumab). Conclusion In this study, larger mean BMD increases and greater BMD responder rates were achieved when romosozumab was used before, versus after, an antiresorptive agent. Since BMD on treatment is a strong surrogate for bone strength and fracture risk, this analysis supports the thesis that initial treatment with romosozumab followed by an antiresorptive will result in greater efficacy versus the reverse sequence.

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Section: Discussionmentioning

confidence: 99%

Romosozumab and antiresorptive treatment: the importance of treatment sequence

et al. 2022

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“…With the increased lifespan of the human population, a higher proportion of the global population will be susceptible to osteoporosis ( 29 – 31 ). It is the current challenge to develop novel strategies to identify the high risk of osteoporosis so that the patients receive the corresponding treatment as early as possible ( 32 – 34 ). In this study, we demonstrated white blood cells level is dynamics and negatively correlated with bone mineral density during the progression of osteoporosis, supporting that routine complete blood count is applied as a potential diagnostic and putative marker for osteoporosis.…”

Section: Discussionmentioning

confidence: 99%

Relationship between indices of circulating blood cells and bone homeostasis in osteoporosis

Hao

Guan

et al. 2022

Front. Endocrinol.

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Bone development have been shown to play an important role in regulating hematopoiesis as one major component of bone marrow microenvironment. Recent studies support the notion that there is an intricate relationship between hematopoiesis and bone homeostasis, however, little is known about the alterations in the hematopoietic lineages in pathologic conditions. Using various osteoporotic mouse models, we show here that bone microarchitecture abnormalities alter parameters of peripheral blood cells. The level of white blood cells is dynamics and negatively correlated with bone mineral density during the progression of osteoporosis. Furthermore, our clinical data confirm that osteoporosis is associated with abnormal circulating blood cell counts. These results demonstrated a causal link that osteoporosis is accompanied by the altered circulating blood cells, supporting the idea of a close interplay between hematopoiesis and bone homeostasis. Our study would propose that routine complete blood count might be applied as a potential diagnostic and putative marker for osteoporosis.

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“…Mechanical testing using the three-point bending method revealed that when subjected to a compressive force, bone strength at the site of PLF was predominantly higher in the R group than that in the C group. Similarly, based on finite 3/6 element analysis using CT images, Jacques et al reported that 1 year of romosozumab treatment followed by alendronate administration increased bone strength in postmenopausal women at high risk of osteoporosis compared with those treated with alendronate only 19 . Furthermore, in a subanalysis of the FRAME study, bone volume and microstructure at 12 months, as assessed by micro-CT, were significantly increased with romosozumab administration 20 .…”

Section: Discussionmentioning

confidence: 99%

Bone union and strength effect of Romosozumab: An imaging and mechanical study using a rat posterolateral lumbar fusion model

Mukaihata

Inage

Kim

et al. 2022

Preprint

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In this study, we investigated the effect of romosozumab on bone strength at the fusion site in rats that underwent posterolateral lumbar fusion. For bone grafting, autogenous bone was harvested from the spinous process and grafted between the intervertebral joint and transverse processes of the 4th, 5th, and 6th lumbar vertebra bilaterally along with 40 mg of demineralized bone matrix. Rats were matched by body weight and divided equally into R (romosozumab, 25 mg/kg) and C (control, saline) groups. Subcutaneous injections were administered twice a week until 10 weeks post-operation. Computed tomography was performed 10 weeks post-operation to measure bone fusion rate, fused bone volume, and bone density. The fused area bone strength was also measured using 3-point bending. Results showed that group R rats had significantly higher bone fusion zone volume, bone mineral density, and bone strength than group C rats. Thus, the results demonstrated that romosozumab administration not only promoted osteogenesis at the bone graft site but also affected bone strength. Conclusion We demonstrated that romosozumab administration not only promoted osteogenesis at the bone graft site but also affected bone strength.

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Romosozumab improves lumbar spine bone mass and bone strength parameters relative to alendronate in postmenopausal women: results from the Active-Controlled Fracture Study in Postmenopausal Women With Osteoporosis at High Risk (ARCH) trial

Cited by 45 publications

References 42 publications

Romosozumab and antiresorptive treatment: the importance of treatment sequence

Romosozumab and antiresorptive treatment: the importance of treatment sequence

Relationship between indices of circulating blood cells and bone homeostasis in osteoporosis

Bone union and strength effect of Romosozumab: An imaging and mechanical study using a rat posterolateral lumbar fusion model

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