Influence of fall environment and fall direction on risk of injury among pre-frail and frail adults Abstract Summary In this prospective study, half of all falls resulted in injury. Pre-frail adults sustained more injuries, while more frail adults had injuries requiring hospitalization or fractures. Pre-frail adults fell more often when in movement compared with frail adults who fell more often when standing and in indoor public spaces. Purpose To assess prospectively how fall environment and direction are related to injury among pre-frail and frail adults. Methods We included 200 community-dwelling adults with a prior fall (pre-frail, mean age 77 years) and 173 adults with acute hip fracture (frail, mean age 84 years; 77% community-dwelling). Falls were prospectively recorded using standardized protocols in monthly intervals, including date, time, fall direction and environment, and injury. We used logistic regression to assess the odds of injury adjusting for age, body mass index (BMI), and gender. Results We recorded 513 falls and 331 fall-related injuries (64.5%) among the 373 participants. While the fall rate was similar between groups, pre-frail adults had more injuries (71% among pre-frail vs. 56% among frail, p = 0.0004) but a lower incidence of major injuries (9% among pre-frail vs. 27% among frail, p = 0.003). Pre-frail adults fell more often while in movement (84% among pre-frail vs. 55% among frail, p < 0.0001), and frail adults fell more often while standing (26% vs. 15% respectively, p = 0.01). The odds of injury among frail adults was increased 3.3-fold when falling sideways (OR = 3.29, 95% CI = 1.68–6.45) and 2.4-fold when falling in an indoor public space (OR = 2.35, 95% CI = 1.00–5.53), and was reduced when falling at home (OR = 0.55, 95% CI = 0.31–0.98). The odds of injury among pre-frail adults was not influenced by environment and was 53% lower when falling backwards (OR = 0.47, 95% CI = 0.26–0.82). Conclusion While pre-frail adults sustain more fall-related injuries, frail adults were more likely to sustain major injuries, especially when falling sideways or outside their home.

Systematic review of the effects of bisphosphonates on bone density and fracture incidence in childhood acute lymphoblastic leukaemia Abstract Summary Skeletal fragility is a common complication of childhood acute lymphoblastic leukaemia (ALL) but the impact of bisphosphonate therapy on bone mass and fracture is unclear. We aim to conduct a systematic review to evaluate the effects of bisphosphonates on bone mineral density (BMD) and fracture incidence in children with ALL. Methods EMBASE, Medline and the Cochrane Library were thoroughly searched by two researchers. Inclusion criteria was any child under the age of 18 years with a diagnosis of ALL, who had received any bisphosphonate treatment and had serial measurements of bone density performed thereafter. All primary research studies of any study design, excluding case reports, were included. Results Ten full text papers were identified with two exclusively meeting the inclusion criteria. Both studies administered bisphosphonates to children receiving maintenance chemotherapy for varying durations. Bone density was assessed at regular intervals by dual x-ray absorptiometry (DXA). The majority of participants had an improvement in bone density at the end of each study. However, no size adjustment of DXA data was performed. Limited information on fracture occurrence was provided by one study but did not include routine screening for vertebral fractures. Conclusions This systematic review identified that there is insufficient evidence to support routine use of prophylactic bisphosphonate therapy in childhood ALL for prevention of fracture and improvement of bone mass. Future well-designed clinical trials in those at highest risk of fractures in ALL are now needed.

Percutaneous vertebroplasty versus non-operative treatment for osteoporotic vertebral compression fractures: a meta-analysis of randomized controlled trials Abstract Purpose Osteoporotic vertebral compression fractures (OVCFs) are common in the elderly population and are often treated using percutaneous vertebroplasty (PVP). However, the effectiveness of PVP reported by various randomized controlled trials (RCTs) is inconclusive. This study aimed to analyze, from published literature, the efficacy and safety of PVP for OVCFs. Methods A search was conducted in Medline, EMBASE, and Cochrane Libraries since their respective inception on January 1, 2019, for RCTs of OVCFs treated with PVP compared with non-operative treatment. The primary outcomes were pain relief at 1 to 2 weeks, 1 to 3 months, and 6 to 12 months. The secondary outcome was the rate of occurrence of new vertebral fractures. Meta-analysis was performed using a random effect model. Results A total of 13 RCTs comprising 1624 patients were included. For the blinded studies, statistical differences were found between PVP and the sham injection group for the 3 primary outcomes in the subgroup of the Vertebroplasty for Acute Painful Osteoporotic fractURes (VAPOUR) trial. Although pain scores were similar between the PVP group and the sham injection group for the VAPOUR trial at each period, the effect size of PVP increased over time. For the open-label studies, PVP significantly reduced pain at all time points. The risk of new vertebral fractures was similar between the PVP groups and control groups. Conclusions Application of PVP was effective and safe only in patients with acute OVCFs having persistent and severe pain. No benefits were recorded, among patients with older fractures or those bearing non-severe symptoms.

Letter to the Editor about the article “A systematic review and meta-analysis of the effect of bisphosphonate drug holidays on bone mineral density and osteoporotic fracture risk”

Fracture prediction from self-reported falls in routine clinical practice: a registry-based cohort study Abstract Summary A simple question construct regarding number of falls in the previous year, ascertained by a single question, was strongly associated with incident fractures in routine clinical practice using a population-based dual-energy X-ray absorptiometry (DXA) registry. Introduction There is conflicting evidence from research cohorts that falls independently increase fracture risk. We examined the independent effects of falls on subsequent fractures in a large clinical registry of bone mineral density (BMD) results for the Province of Manitoba, Canada that has been systematically collecting self-reported falls information since September 1, 2012. Methods The study population consisted of 24,943 women and men aged 40 years and older (mean age 65.5 ± 10.2 years) with fracture probability assessment (FRAX), self-reported falls for the previous year (categorized as none, 1, 2, or > 3) and fracture outcomes. Adjusted hazard ratios (HR) with 95 confidence intervals (CI) for time to fracture were estimated using Cox proportional hazards models. Results During mean observation time of 2.7 ± 1.0 years, 863 (3.5%) sustained one or more major osteoporotic fractures (MOF), 212 (0.8%) sustained a hip fracture, and 1210 (4.9%) sustained any incident fracture. Compared with no falls in the previous year (referent), there was a gradient of increasing risk for fracture with increasing number of falls (all P < 0.001). Results showed minimal attenuation with covariate adjustment. When adjusted for baseline fracture probability (FRAX score with BMD) the HR for MOF increased from 1.49 (95% CI 1.25–1.78) for one fall to 1.74 (1.33–2.27) for two falls to 2.62 (2.06–3.34) for ≥ 3 falls. HRs were similar for any incident fracture and slightly greater for prediction of hip fracture, reaching 3.41 (95% CI 2.19–5.31) for ≥ 3 previous falls. Conclusions Self-report number of falls in the previous year is strongly associated with incident fracture risk in the routine clinical practice setting, and this risk is independent of age, sex, BMD, and baseline fracture probability. Moreover, there is dose–response with multiple falls (up to a maximum of 3) conferring greater risk than a single fall.

Evaluation of bone texture imaging parameters on panoramic radiographs of patients with Sheehan’s syndrome: a STROBE-compliant case-control study Abstract Summary Sheehan’s syndrome (SHS) is a rare condition related to the risk of osteoporosis and evaluation of bone texture imaging features on panoramic radiographs would be suitable for this condition, which was the aim of the present study. Fractal dimension, lacunarity, and trabecular morphologic aspects were significantly altered in these patients. Introduction SHS is an important public health problem particularly in developing countries. It is characterized as postpartum hypopituitarism secondary to obstetric complications-related ischemic pituitary necrosis that shows significant systemic metabolic repercussions. Thus, this study aimed to evaluate bone texture parameters in digital panoramic radiographs of patients with SHS. Methods A case-control study was conducted with 30 SHS patients from an Endocrinology and Diabetology Service of reference in Brazil, and 30 age- and sex-matched healthy controls. A custom computer program measured fractal dimension, lacunarity, and some morphologic features in the following mandibular regions of interest (50 × 50 pixels): below the mental foramen (F1), between the first and second molars (M1), and at the center of the mandibular ramus (R1). Results The fractal analysis showed a statistically significant difference between the studied groups in all regions of interest. The fractal dimension in F1 (p = 0.016), M1 (p = 0.043), and R1 (p = 0.028) was significantly lower in SHS group, as well as lacunarity in R1 (p = 0.008). Additionally, several morphologic features were statistically significant in the SHS group (p < 0.05). Conclusion Therefore, individuals with SHS showed altered imaging texture parameters on panoramic radiographs, which reflect a smaller spatial organization of the bone trabeculae and, possibly, a state of reduced mineral bone density.

Effects of milk powder intervention on bone mineral density and indicators related to bone metabolism in Chinese adolescents Abstract Summary The study is to determine the effects of milk powder on bone density and metabolism in healthy adolescents. Vitamin D and calcium supplements increased IGF-1 but did not affect bone mineralization or turnover. Higher vitamin D in combination with sufficient calcium supplementation in such populations requires attention. Introduction Both calcium and vitamin D play an important role in bone mineralization in adolescents. Methods In this one and a half-year randomized controlled trial, 232 participants (aged 12–15 years) were randomly assigned to three intervention groups receiving milk powder fortified with vitamin D 400 IU plus calcium 300, or 600, or 900 mg [Ca3D (n = 54), Ca6D (n = 56), and Ca9D (n = 49)], or one control group maintaining habitual diet [control (n = 73)]. Bone turnover markers, serum intact PTH, 25(OH)D, and IGF-1 levels were measured at baseline and one and a half years, and bone mineral contents and bone areal mineral density were measured by Dual-energy X-ray absorptiometry (DXA) at baseline, one year, and one and a half years. Results Baseline average serum 25(OH)D level and calcium intake were 29.4 nmol/L and 363.5 mg/day, respectively. There was a significant increase in bone turnover, total body, hip, lumbar spine bone mineral density (BMD), and total body BMC as well as slight fluctuations in 25(OH)D levels over one and a half years without between-group differences. Significantly decreased serum PTH level was only observed in the Ca6D group (31%, p < 0.0001), in which the intervention effect was also significant (p = 0.0029) compared with the control group. IGF-1 levels increased significantly in all intervention groups (18.5 to 22.8%, p < 0.05) but decreased in the control group (16.5%, p < 0.05), and the group by time interaction was also significant (p = 0.0029). Conclusions Our study showed that in healthy adolescents with low vitamin D status and calcium intake, mild vitamin D and mild to modest calcium supplements increased IGF-1 but did not affect bone mineralization or turnover. Higher vitamin D in combination with sufficient calcium supplementation in such populations requires attention.

Professor Howard A. Morris

Reply to “Antiretroviral therapy options in people living with HIV at risk of or with osteoporosis. Comment on: Diagnosis, prevention, and treatment of bone fragility in people living with HIV: a position statement from the Swiss Association against Osteoporosis” by S. Noe, H. Jaeger, E. Wolf

Antiretroviral therapy options in people living with HIV at risk of or with osteoporosis