Multimorbidity clusters potentially superior to individual diseases for stratifying fracture risk in older people: a nationwide cohort study.

RATIONALE: Comorbidities are common in fracture patients, but the interaction between fracture and comorbidities remains unclear. This study aimed to define specific multimorbidity clusters in older adults and quantify the association between the multimorbidity clusters and fracture risk. METHODS: This nationwide cohort study includes 1.7 million adults in Denmark aged ≥50 years who were followed from 2001 through 2014 for an incident low-trauma fracture. Chronic diseases and fractures were identified from the Danish National Hospital Discharge Register. Latent class analysis and Cox's regression were conducted to define the clusters and quantify fracture risk, respectively. RESULTS: The study included 793 815 men (age: 64 ± 10) and 873 524 women (65.5 ± 11), with a third having ≥1 chronic disease. The pre-existent chronic diseases grouped individuals into low-multimorbidity (80.3% in men, 83.6% in women), cardiovascular (12.5%, 10.6%), malignant (4.1%, 3.8%), diabetic (2.4%, 2.0%) and hepatic clusters (0.7%, men only). These clusters distinguished individuals with advanced, complex, or late-stage disease from those having earlier-stage disease. During a median follow-up of 14 years (IQR: 6.5, 14), 95 372 men and 212 498 women sustained an incident fracture. The presence of multimorbidity was associated with a significantly greater risk of fracture, independent of age and sex. Importantly, the multimorbidity clusters had the highest discriminative performance in assessing fracture risk, whereas the strength of their association with fracture risk equalled or exceeded that of both the individual chronic diseases most prevalent in each cluster and of counts-based comorbidity indices. CONCLUSIONS: Future fracture prevention strategies should take comorbidities into account. Multimorbidity clusters may provide greater insight into fracture risk than individual diseases or counts-based comorbidity indices.

Sex-differential testosterone response to long-term weight loss.

OBJECTIVES: Obesity-associated gonadal dysfunction is a common comorbidity in patients seeking weight loss interventions. We examined the incremental effect of weight loss on gonadal axes in men and women over 3 years. Changes in sex hormones were compared between dietary intervention (Diet) and bariatric procedures: Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG) and laparoscopic adjustable gastric banding (LAGB). Additional analysis assessed changes in corticotropic, somatotropic and thyroid axes after weight loss interventions. METHODS: This prospective, observational study included 61 adults with Body Mass Index >30 kg/m2, mean age 51 (SD = 11) years. Endocrine parameters were measured at baseline and at 6 timepoints over 36-months. RESULTS: For each 1 kg of weight lost, between baseline and 36 months, total testosterone increased by 0.6% (95% CI: 0.2%, 1.0%, p = 0.002) in males and decreased by 0.8% (95% CI: -1.4%, -0.3%, p = 0.003) in females. These changes remained statistically significant when controlled for age and for menopausal status in females. At 36 months, in comparison with Diet, RYGB women had lower total testosterone by 54% (95% CI: -90%, -17%, p = 0.004), reduced free androgen index (FAI) by 65% (95% CI; -114%, -17%, p = 0.009) while SG had reduced FAI by 39% (95% CI; -77%, 0%, p = 0.05). No such differences between groups were noted for male subjects. Adrenocorticotropic hormone declined by 0.3% (95% CI: 0.0, -0.5%, p = 0.05), insulin-like growth factor-1 increased by 0.4% (95% CI; 0.2%, 0.7%, p = 0.005), without such thyrotrophin change for each 1 kg of weight loss, for entire cohort, over 36 months. CONCLUSIONS: The testosterone changes observed in this study were proportional to the amount of weight loss. In females, reduction in androgens was independent of age and menopausal status and more pronounced after bariatric procedures. This study finding warrants further clinical research to explore an impact of androgen reduction on functional and cognitive status in postmenopausal women. The observed changes in pituitary hormones may contribute to the metabolic benefits of bariatric surgery.

Measurement of Spiritual Wellbeing in an Australian Hospital Population Using the Functional Assessment of Chronic Illness Therapy: Spiritual Wellbeing Scale (FACIT-Sp-12).

Spiritual wellbeing is known to be a predictor of increased patient coping in hospital settings. Therefore, access to a valid and reliable measure of spiritual wellbeing amongst general hospital patients is highly recommended. The aim of this study was to investigate the dimensionality, reliability, and validity of the Functional Assessment of Chronic Illness Therapy Spiritual Wellbeing scale (FACIT-Sp-12) in a heterogeneous cohort of hospital patients. A cross-sectional survey was administered to 897 adult patients across six hospitals in Sydney, Australia. Confirmatory factor analysis for the three-factor FACIT-12-Sp indicated a poor fit, but after removal of Item 12, the three-factor FACIT-11-Sp presented a good fit to the data. Reliability testing indicated acceptable to good internal consistency. Validity was supported by statistically significant differences between patients who considered themselves 'both spiritual and religious' and 'not religious or spiritual'. While some caution should be taken when using the FACIT-Sp due to several limitations, nevertheless, in a general hospital population in Australia, the three-factor FACIT-11-Sp indicated good dimensionality, reliability, and validity.

A meta-analysis of previous falls and subsequent fracture risk in cohort studies.

The relationship between self-reported falls and fracture risk was estimated in an international meta-analysis of individual-level data from 46 prospective cohorts. Previous falls were associated with an increased fracture risk in women and men and should be considered as an additional risk factor in the FRAX® algorithm. INTRODUCTION: Previous falls are a well-documented risk factor for subsequent fracture but have not yet been incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between previous falls and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD). METHODS: The resource comprised 906,359 women and men (66.9% female) from 46 prospective cohorts. Previous falls were uniformly defined as any fall occurring during the previous year in 43 cohorts; the remaining three cohorts had a different question construct. The association between previous falls and fracture risk (any clinical fracture, osteoporotic fracture, major osteoporotic fracture, and hip fracture) was examined using an extension of the Poisson regression model in each cohort and each sex, followed by random-effects meta-analyses of the weighted beta coefficients. RESULTS: Falls in the past year were reported in 21.4% of individuals. During a follow-up of 9,102,207 person-years, 87,352 fractures occurred of which 19,509 were hip fractures. A previous fall was associated with a significantly increased risk of any clinical fracture both in women (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.33-1.51) and men (HR 1.53, 95% CI 1.41-1.67). The HRs were of similar magnitude for osteoporotic, major osteoporotic fracture, and hip fracture. Sex significantly modified the association between previous fall and fracture risk, with predictive values being higher in men than in women (e.g., for major osteoporotic fracture, HR 1.53 (95% CI 1.27-1.84) in men vs. HR 1.32 (95% CI 1.20-1.45) in women, P for interaction = 0.013). The HRs associated with previous falls decreased with age in women and with duration of follow-up in men and women for most fracture outcomes. There was no evidence of an interaction between falls and BMD for fracture risk. Subsequent risk for a major osteoporotic fracture increased with each additional previous fall in women and men. CONCLUSIONS: A previous self-reported fall confers an increased risk of fracture that is largely independent of BMD. Previous falls should be considered as an additional risk factor in future iterations of FRAX to improve fracture risk prediction.