Ebeling, Peter R

ImportanceFalls and fractures are frequent and deleterious to the health of older people. Aspirin has been reported to reduce bone fragility and slow bone loss.ObjectiveTo determine if daily low-dose aspirin (100 mg) reduces the risk of fractures or serious falls (fall-related hospital presentations) in healthy older men and women.Design, Setting, and ParticipantsThis substudy of a double-blind, randomized, placebo-controlled trial studied older adult men and women in 16 major sites across southeastern Australia. The ASPREE-FRACTURE substudy was conducted as part of the Australian component of the ASPREE trial. Between 2010 and 2014 healthy (free of cardiovascular disease, dementia or physical disability), community-dwelling volunteers aged 70 years or older were recruited to participate in the ASPREE trial. Potentially eligible participants were identified by medical practitioners and trial personnel and were then sent a letter of invitation to participate. Interested participants were screened for suitability. Eligible participants with medical practitioner authorization and adherent to a 4-week run-in medication trial were randomized. Data were analyzed from October 17, 2019, to August 31, 2022.InterventionsParticipants in the intervention group received a daily dose of oral 100 mg enteric-coated (low-dose) aspirin. The control group received a daily identical enteric-coated placebo tablet.Main Outcomes and MeasuresThe primary outcome of ASPREE-FRACTURE was the occurrence of any fracture. The secondary outcome was serious fall resulting in hospital presentation.ResultsIn total, 16 703 people with a median (IQR) age of 74 (72-78) years were recruited, and 9179 (55.0%) were women. There were 8322 intervention participants and 8381 control participants included in the primary and secondary outcome analysis of 2865 fractures and 1688 serious falls over the median follow-up of 4.6 years. While there was no difference in the risk of first fracture between the intervention and control participants (hazard ratio, 0.97; 95% CI, 0.87-1.06; P = .50), aspirin was associated with a higher risk of serious falls (total falls 884 vs 804; incidence rate ratio, 1.17; 95% CI, 1.03-1.33; P = .01). Results remained unchanged in analyses that adjusted for covariates known to influence fracture and fall risk.Conclusions and RelevanceIn this substudy of a randomized clinical trial, the failure of low-dose aspirin to reduce the risk of fractures while increasing the risk of serious falls adds to evidence that this agent provides little favorable benefit in a healthy, White older adult population.Trial RegistrationThis substudy is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615000347561).

ABSTRACT Vertebral augmentation is among the current standards of care to reduce pain in patients with vertebral fractures (VF), yet a lack of consensus regarding efficacy and safety of percutaneous vertebroplasty and kyphoplasty raises questions on what basis clinicians should choose one therapy over another. Given the lack of consensus in the field, the American Society for Bone and Mineral Research (ASBMR) leadership charged this Task Force to address key questions on the efficacy and safety of vertebral augmentation and other nonpharmacological approaches for the treatment of pain after VF. This report details the findings and recommendations of this Task Force. For patients with acutely painful VF, percutaneous vertebroplasty provides no demonstrable clinically significant benefit over placebo. Results did not differ according to duration of pain. There is also insufficient evidence to support kyphoplasty over nonsurgical management, percutaneous vertebroplasty, vertebral body stenting, or KIVA®. There is limited evidence to determine the risk of incident VF or serious adverse effects (AE) related to either percutaneous vertebroplasty or kyphoplasty. No recommendation can be made about harms, but they cannot be excluded. For patients with painful VF, it is unclear whether spinal bracing improves physical function, disability, or quality of life. Exercise may improve mobility and may reduce pain and fear of falling but does not reduce falls or fractures in individuals with VF. General and intervention-specific research recommendations stress the need to reduce study bias and address methodological flaws in study design and data collection. This includes the need for larger sample sizes, inclusion of a placebo control, more data on serious AE, and more research on nonpharmacologic interventions. Routine use of vertebral augmentation is not supported by current evidence. When it is offered, patients should be fully informed about the evidence. Anti-osteoporotic medications reduce the risk of subsequent vertebral fractures by 40–70%. © 2018 American Society for Bone and Mineral Research.

Background Disability, mortality and healthcare burden from fractures in older people is a growing problem worldwide. Observational studies suggest that aspirin may reduce fracture risk. While these studies provide room for optimism, randomised controlled trials are needed. This paper describes the rationale and design of the ASPirin in Reducing Events in the Elderly (ASPREE)-Fracture substudy, which aims to determine whether daily low-dose aspirin decreases fracture risk in healthy older people. Methods ASPREE is a double-blind, randomised, placebo-controlled primary prevention trial designed to assess whether daily active treatment using low-dose aspirin extends the duration of disability-free and dementia-free life in 19 000 healthy older people recruited from Australian and US community settings. This substudy extends the ASPREE trial data collection to determine the effect of daily low-dose aspirin on fracture and fall-related hospital presentation risk in the 16 500 ASPREE participants aged ≥70 years recruited in Australia. The intervention is a once daily dose of enteric-coated aspirin (100 mg) versus a matching placebo, randomised on a 1:1 basis. The primary outcome for this substudy is the occurrence of any fracture—vertebral, hip and non-vert-non-hip—occurring post randomisation. Fall-related hospital presentations are a secondary outcome. Discussion This substudy will determine whether a widely available, simple and inexpensive health intervention—aspirin—reduces the risk of fractures in older Australians. If it is demonstrated to safely reduce the risk of fractures and serious falls, it is possible that aspirin might provide a means of fracture prevention. Trial registration number The protocol for this substudy is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615000347561).

Abstract We measured type I procollagen carboxyl-terminal propeptide (PICP) by a commercial radioimmunoassay and amino-terminal propeptide (PINP) by an enzyme-linked immunosorbent assay (ELISA) developed in our laboratory in serum from 75 normal women, 10 growing girls, 84 normal men, and 197 patients with various metabolic bone diseases. The molar concentrations of serum PINP were 100-fold higher than those of PICP, suggesting differences in the metabolism of PICP and PINP. In normal women, serum PICP values correlated positively with age and serum PINP values correlated negatively with age (r = 0.28 and −0.32, respectively; P = 0.02). In normal men, however, PICP correlated negatively with age (r = −0.32, P = 0.003) whereas PINP did not change. As assessed by Z scores (SD from age- and sex-specific predicted normal mean), changes in serum PICP and PINP values were concordant in hypoparathyroidism (mean Z scores for PICP and PINP, −0.63 and −1.48, respectively) and Cushing's syndrome (0.50 and 0.40) but were discordant in acromegaly (0.78 and −0.68), hyperthyroidism (1.33 and −0.66), untreated postmenopausal osteoporosis (-0.11 and 0.40), fluoride-treated postmenopausal osteoporosis (-0.61 and 1.08), Paget's disease (4.05 and −0.20), and chronic renal failure (1.45 and −0.50). With either assay, deviations from normal were less pronounced than the deviations of concurrently measured serum osteocalcin and bone alkaline phosphatase values. The deviations in these latter two values agreed better with those of PICP than with those of PINP, except in untreated or fluoride-treated osteoporotic patients. We conclude that for assessing abnormalities in bone formation in metabolic bone diseases, assays for serum PICP or PINP generally are inferior to those for serum osteocalcin and bone alkaline phosphatase.