Impact of osteoporosis and osteoporosis medications on fracture healing: a narrative review

Summary: Antiresorptive medications do not negatively affect fracture healing in humans. Teriparatide may decrease time to fracture healing. Romosozumab has not shown a beneficial effect on human fracture healing. Background: Fracture healing is a complex process. Uncertainty exists over the influence of osteoporosis and the medications used to treat it on fracture healing. Methods: Narrative review authored by the members of the Fracture Working Group of the Committee of Scientific Advisors of the International Osteoporosis Foundation (IOF), on behalf of the IOF and the Société Internationale de Chirurgie Orthopédique et de Traumatologie (SICOT). Results: Fracture healing is a multistep process. Most fractures heal through a combination of intramembranous and endochondral ossification. Radiographic imaging is important for evaluating fracture healing and for detecting delayed or non-union. The presence of callus formation, bridging trabeculae, and a decrease in the size of the fracture line over time are indicative of healing. Imaging must be combined with clinical parameters and patient-reported outcomes. Animal data support a negative effect of osteoporosis on fracture healing; however, clinical data do not appear to corroborate with this. Evidence does not support a delay in the initiation of antiresorptive therapy following acute fragility fractures. There is no reason for suspension of osteoporosis medication at the time of fracture if the person is already on treatment. Teriparatide treatment may shorten fracture healing time at certain sites such as distal radius; however, it does not prevent non-union or influence union rate. The positive effect on fracture healing that romosozumab has demonstrated in animals has not been observed in humans. Conclusion: Overall, there appears to be no deleterious effect of osteoporosis medications on fracture healing. The benefit of treating osteoporosis and the urgent necessity to mitigate imminent refracture risk after a fracture should be given prime consideration. It is imperative that new radiological and biological markers of fracture healing be identified. It is also important to synthesize clinical and basic science methodologies to assess fracture healing, so that a convergence of the two frameworks can be achieved

Severe osteoporosis: diagnosis and follow-up. Lessons for clinical practice

The management of osteoporosis has improved considerably, leading to the development of new goals. A major concern today is the management of patients with severe osteoporosis, in whom the need for pharmacotherapy is clear [1]. Epidemiological data have established that osteoporosis is associated with severe complications [2,3]. Furthermore, osteoporosis is now recognized as a complication of several chronic diseases, whose presence adversely affects the management of osteoporosis. The ODISSEE task force (Osteoporosis DIagnosis and Surveillance of SEvErity) was established to answer practical questions regarding the management of severe osteoporosis, based on evidence in the literature. Several groups conducted an exhaustive literature review, and advice was obtained from a panel of French rheumatologists. The ODISSEE scientific committee then developed the first consensus statement on the diagnosis, follow-up and management of severe osteoporosis. This statement was validated by a panel of 70 French rheumatologists at the first national ODISSEE meeting held on November 13-14, 2009

Impact of osteoporosis and osteoporosis medications on fracture healing: a narrative review

UNLABELLED Antiresorptive medications do not negatively affect fracture healing in humans. Teriparatide may decrease time to fracture healing. Romosozumab has not shown a beneficial effect on human fracture healing. BACKGROUND Fracture healing is a complex process. Uncertainty exists over the influence of osteoporosis and the medications used to treat it on fracture healing. METHODS Narrative review authored by the members of the Fracture Working Group of the Committee of Scientific Advisors of the International Osteoporosis Foundation (IOF), on behalf of the IOF and the Société Internationale de Chirurgie Orthopédique et de Traumatologie (SICOT). RESULTS Fracture healing is a multistep process. Most fractures heal through a combination of intramembranous and endochondral ossification. Radiographic imaging is important for evaluating fracture healing and for detecting delayed or non-union. The presence of callus formation, bridging trabeculae, and a decrease in the size of the fracture line over time are indicative of healing. Imaging must be combined with clinical parameters and patient-reported outcomes. Animal data support a negative effect of osteoporosis on fracture healing; however, clinical data do not appear to corroborate with this. Evidence does not support a delay in the initiation of antiresorptive therapy following acute fragility fractures. There is no reason for suspension of osteoporosis medication at the time of fracture if the person is already on treatment. Teriparatide treatment may shorten fracture healing time at certain sites such as distal radius; however, it does not prevent non-union or influence union rate. The positive effect on fracture healing that romosozumab has demonstrated in animals has not been observed in humans. CONCLUSION Overall, there appears to be no deleterious effect of osteoporosis medications on fracture healing. The benefit of treating osteoporosis and the urgent necessity to mitigate imminent refracture risk after a fracture should be given prime consideration. It is imperative that new radiological and biological markers of fracture healing be identified. It is also important to synthesize clinical and basic science methodologies to assess fracture healing, so that a convergence of the two frameworks can be achieved

Poor Bone Quality is Associated With Greater Arterial Stiffness: Insights From the UK Biobank

Osteoporosis and ischemic heart disease (IHD) represent important public health problems. Existing research suggests an association between the two conditions beyond that attributable to shared risk factors, with a potentially causal relationship. In this study, we tested the association of bone speed of sound (SOS) from quantitative heel ultrasound with (i) measures of arterial compliance from cardiovascular magnetic resonance (aortic distensibility [AD]); (ii) finger photoplethysmography (arterial stiffness index [ASI]); and (iii) incident myocardial infarction and IHD mortality in the UK Biobank cohort. We considered the potential mediating effect of a range of blood biomarkers and cardiometabolic morbidities and evaluated differential relationships by sex, menopause status, smoking, diabetes, and obesity. Furthermore, we considered whether associations with arterial compliance explained association of SOS with ischemic cardiovascular outcomes. Higher SOS was associated with lower arterial compliance by both ASI and AD for both men and women. The relationship was most consistent with ASI, likely relating to larger sample size available for this variable (n = 159,542 versus n = 18,229). There was no clear evidence of differential relationship by menopause, smoking, diabetes, or body mass index (BMI). Blood biomarkers appeared important in mediating the association for both men and women, but with different directions of effect and did not fully explain the observed effects. In fully adjusted models, higher SOS was associated with significantly lower IHD mortality in men, but less robustly in women. The association of SOS with ASI did not explain this observation. In conclusion, our findings support a positive association between bone and vascular health with consistent patterns of association in men and women. The underlying mechanisms are complex and appear to vary by sex

An appraisal of golimumab in the treatment of severe, active nonradiographic axial spondyloarthritis

Julien Paccou, René-Marc Flipo Department of Rheumatology, Lille University Hospital, Lille, France Abstract: Golimumab (Simponi®) is a fully human tumor necrosis factor α inhibitor (TNFi) antibody administered subcutaneously. In the European Union, golimumab is indicated for the treatment of adults with severe, active axial spondyloarthritis (axSpA), which includes both ankylosing spondylitis (AS) and nonradiographic axSpA (nr-axSpA). In the US, it is indicated for the treatment of adults with active AS only. This article reviews the efficacy and tolerability of golimumab in nr-axSpA patients compared to other TNFi agents (adalimumab, infliximab, etanercept, and certolizumab pegol). In one ongoing, well-designed controlled study (GO-AHEAD), data at 16 weeks showed that treatment with golimumab (50 mg every 4 weeks) was effective in improving the clinical signs and symptoms of disease in nr-axSpA patients. In addition, 16 weeks of treatment with golimumab reduced inflammation in the sacroiliac joints and spine in patients with nr-axSpA. Moreover, objective evidence of active inflammation at baseline, such as a positive magnetic resonance imaging scan and/or an elevated CRP level, was a good predictor of treatment response to golimumab. Golimumab was generally well tolerated in this study, with a tolerability profile consistent with that seen in previous clinical trials for other indications. Although additional long-term data are needed, current evidence indicates that golimumab is an effective option for the treatment of nr-axSpA. However, in the absence of comparative head-to-head trials, there is no recommended hierarchy for the first prescription of a TNFi agent for the treatment of either nr-axSpA or AS. Keywords: axial spondyloarthritis, nonradiographic axial spondyloarthritis, ankylosing spondylitis, golimumab, tumor necrosis factor α inhibitor, therap