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Bisphosphonate use in childhood raises BMD, physical activity in osteogenesis imperfecta
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For patients with osteogenesis imperfecta, starting IV bisphosphonate therapy in childhood may result in higher bone mineral density and greater physical activity levels than if the treatment is not initiated until adulthood, according to a study published in Bone.
“Bisphosphonates have been demonstrated to improve BMD and have beneficial effects on function and quality of life in the short term in many studies,” Andrew G. Feehan, MD, a medical intern at The Royal Melbourne Hospital in Victoria, Australia, told Endocrine Today. “However, long-term benefits have been largely anecdotal. In our study, we have shown beneficial effects in our cohort 20-plus years after starting bisphosphonate therapy. While bisphosphonates do not alter the underlying pathophysiology in [osteogenesis imperfecta], they effectively harden bone, perhaps explaining the higher physical activity levels observed.”
From February to August 2017, researchers recruited 52 participants from The Royal Children’s Hospital Melbourne or from the practice of a study author for a cross-sectional comparative study of two cohorts. All participants were older than 18 years and had a clinical and/or genetic diagnosis of osteogenesis imperfecta. The first cohort included participants who had received at least one infusion of bisphosphonate treatment at The Royal Children’s Hospital Melbourne before age 18 years (n = 33; mean age, 24 years; 45.5% women) The second cohort was the control group, made up of patients who had not been treated with bisphosphonates before age 18 years (n = 19; mean age, 40 years; 68.4% women).
All participants completed four questionnaires. The first questionnaire allowed participants to provide demographic information and fracture and treatment history. Researchers examined quality of life using the WHOQOL-BREF questionnaire, which assesses patients’ physical health, psychological health, social relationships and environment. The third questionnaire dealt with physical activity, with the fourth providing musculoskeletal function data. Researchers also reviewed medical records and recorded the data in the following categories: fracture history, BMD results and bisphosphonate treatment. Duration of bisphosphonate therapy was similar between the groups (7 years vs. 6 years), and median age at initiation was 9 years for the childhood-treated cohort vs. 28 years for the adult-treated cohort (P < .001). Researchers compared the treated and nontreated cohorts through chi-square tests.
Median number of lifetime fractures was similar in both cohorts, with 25 factures (interquartile range [IQR], 7-50) in the childhood-treated group and 30 fractures (IQR, 8.5-55) in the adult-treated group. For all disease severities, the childhood-treated cohort experienced fewer prepubertal fractures. For those with less severe disease, the fracture rate was 5.2 fractures (95% CI, 4-6.5) per 10 person-years vs. 8.3 fractures (95% CI, 6.2-10.8) per 10 person-years in the adult-treated cohort (P = .01). For patients with more severe disease, the fracture rate was 21.8 fractures (95% CI, 20.1-23.5) per 10 person-years in the childhood-treated cohort vs. 36.5 fractures (95% CI, 33.3-39.9) per 10 person-years in the adult-treated cohort (P < .001). The majority of recent fractures in the childhood cohort had been caused by impact, whereas recent fractures were more frequently caused by minimal trauma in the adult-treated cohort.
In addition, researchers found that lumbar spine BMD was higher in the childhood-treated cohort than the adult-treated cohort (z score, –0.4 at mean age 21.3 years vs. –1.9 at mean age 40.9 years; P = .005).
Furthermore, participants in the childhood-treated cohort with less severe osteogenesis imperfecta reported participating in more physical activity than the adult-treated cohort (2,079.5 metabolic equivalent minutes per week vs. 838.5 metabolic equivalent minutes per week; P = .004).
Researchers found no differences in quality-of-life scores between the two cohorts.
Further research is required to determine the effect that bisphosphonate treatment has on the progression of scoliosis in osteogenesis imperfecta, according to Feehan.
“We only investigated the incidence of scoliosis, which we report to be similar to pre-bisphosphonate incidence. However, we do not know whether there is any difference in the severity of scoliosis or the progression of scoliosis within an individual,” Feehan said. – by Melissa J. Webb
For more information:
Andrew G. Feehan, MD, can be reached at agfeehan@me.com.
Disclosures: The authors report no relevant financial disclosures.
Perspective
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The results of this study by Feehan and colleagues are comforting because they reinforce current practice, but they should be interpreted cautiously because methodologic limitations prevent much from being inferred. The difficulty in studying osteogenesis imperfecta is that there is an enormous amount of heterogeneity in the disease. Many different pathogenic mutations can cause osteogenesis imperfecta, and even within a single family, where affected family members share the same mutation, severity of the manifestations can vary widely. A small study cannot guarantee that the groups were really equal at entry in terms of how severely affected they were. Contrary results would have been subject to the same limitations regarding study size and matching between groups. Although most experts believe the basic thrust of what Feehan and colleagues report, which is that patients do better after bisphosphonate treatment, the evidence base for this claim is actually not particularly strong. The results reported here can serve as one more thing that reassures physicians that they’re doing the right thing with usual practice.
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