Kerry E. Broe

A Higher Dose of Vitamin D Reduces the Risk of Falls in Nursing Home Residents: A Randomized, Multiple-Dose Study

OBJECTIVES: To determine the effect of four vitamin D supplement doses on falls risk in elderly nursing home residents.

Vascular calcification in middle-age and long term risk of hip fracture: The Framingham Study

Osteoporosis and atherosclerosis frequently occur in the same individuals and may share similar pathogenic mechanisms. This study examined the relation between severity of aortic calcification in middle‐age years and subsequent risk of hip fracture in women and men in the population‐based Framingham Study.

Protective effect of high protein and calcium intake on the risk of hip fracture in the framingham offspring cohort

The effect of protein on bone is controversial, and calcium intake may modify proteins effect on bone. We evaluated associations of energy‐adjusted tertiles of protein intake (ie, total, animal, plant, animal/plant ratio) with incident hip fracture and whether total calcium intake modified these associations in the Framingham Offspring Study. A total of 1752 men and 1972 women completed a baseline food frequency questionnaire (1991–1995 or 1995–1998) and were followed for hip fracture until 2005. Hazard ratios (HRs) were estimated using Cox proportional hazards regression adjusting for confounders. Baseline mean age was 55 years (SD 9.9 years, range 26 to 86 years). Forty‐four hip fractures occurred over 12 years of follow‐up. Owing to significant interaction between protein (total, animal, animal/plant ratio) and calcium intake (p interaction range = .03 to .04), stratified results are presented. Among those with calcium intakes less than 800 mg/day, the highest tertile (T3) of animal protein intake had 2.8 times the risk of hip fracture [HR = 2.84, 95% confidence interval (CI) 1.20–6.74, p = .02] versus the lowest tertile (T1, p trend = .02). In the 800 mg/day or more group, T3 of animal protein had an 85% reduced hip fracture risk (HR = 0.15, 95% CI 0.02–0.92, p = .04) versus T1 (p trend = .04). Total protein intake and the animal/plant ratio were not significantly associated with hip fracture (p range = .12 to .65). Our results from middle‐aged men and women show that higher animal protein intake coupled with calcium intake of 800 mg/day or more may protect against hip fracture, whereas the effect appears reversed for those with lower calcium intake. Calcium intake modifies the association of protein intake and the risk of hip fracture in this cohort and may explain the lack of concordance seen in previous studies.

Survival of Aged Nursing Home Residents With Hip Fracture

BACKGROUND Little is known about mortality in nursing home residents with hip fracture. This study examined the effect of pre-fracture characteristics, hospital complications, and post-fracture complications on mortality in residents with hip fracture. METHODS This is a retrospective cohort study of 195 long-term care residents (153 women, 42 men) with hip fracture (1999-2006) followed for mortality until June 30, 2007. Pre-fracture characteristics (age, sex, cognition, functional status, comorbidities, body mass index), hospital complications (acute myocardial infarction, congestive heart failure, delirium, infection) and 6-month complications (delirium, pneumonia, pressure ulcer, urinary tract infection [UTI]) were evaluated as potential predictors of mortality. RESULTS During a median follow-up of 1.4 years, 150 participants (76.9%) died. Male residents were nearly twice as likely to die compared with female residents (hazard ratio [HR] = 1.9, 95% confidence interval [CI] 1.2-3.0). Other pre-fracture characteristics associated with increased mortality included older age (HR per 5 years = 1.3, 95% CI 1.1-1.6), low functional status (HR = 1.7, 95% CI 1.0-3.0), anemia (HR = 1.6, 95% CI 1.1-2.5), and coronary artery disease (HR = 2.0, 95% CI 1.3-2.9). Mortality was 70% greater among residents with a pressure ulcer or pneumonia within 6 months of hip fracture (pressure ulcer, HR = 1.7, 95% CI 1.2-2.6; pneumonia, HR = 1.7, 95% CI 1.1-2.7). Individual hospital complications and post-fracture delirium and UTI were not significant predictors of mortality. CONCLUSIONS In addition to pre-fracture characteristics, potentially modifiable post-fracture complications including pressure ulcer and pneumonia were associated with increased mortality in nursing home residents with hip fracture. Prevention strategies to reduce pressure ulcers and pneumonia may help reduce mortality in this frail population.

Predicting fractures using bone mineral density: a prospective study of long-term care residents

Abstract: Bone mineral density (BMD) has been shown to predict fracture risk in community-dwelling older persons; however, no comparable prospective study has been performed in the long-term care setting where the role of BMD testing is uncertain. To determine the ability of a single BMD measurement to predict the risk of subsequent fracture in long-term care residents, we designed a prospective study in a 725-bed long-term care facility. A total of 252 Caucasian nursing home residents (mean age 88 years, 74% women) were recruited between 1992 and 1998. BMD of the hip, radius or both sites was measured using dual-energy X-ray absorptiometry. Participants were followed through September 1999 for the occurrence of fracture. Cox proportional hazards regression models were constructed to determine the relationship between BMD and the risk of fracture controlling for potentially confounding variables. Sixty-three incident osteoporotic fractures occurred during a median follow-up time of 2.3 years. The multivariate-adjusted risk of fracture for each standard deviation decrease in BMD was 2.82 (95% CI 1.81–4.42) at the total hip, 2.79 (95% CI 1.69–4.61) at the femoral neck, 2.26 (95% CI 1.51–3.38) at the trochanter, 1.83 (95% CI 1.14–2.94) at the radial shaft and 1.84 (95% CI 1.21–2.80) at the ultradistal radius. Subjects in the lowest age-specific quartile of femoral neck BMD had over 4 times the incidence of fracture compared with those in the highest quartile. BMD at either hip or radius was a predictor of osteoporotic fracture, although in women, radial BMD did not predict fracture. Knowledge of BMD in long-term care residents provides important information on subsequent fracture risk.

Increased Plasma Osteoprotegerin Concentrations Are Associated with Indices of Bone Strength of the Hip

OBJECTIVE Osteoprotegerin (OPG) is an important regulator of bone turnover through its effects on osteoclastogenesis, yet findings from previous studies of circulating OPG and commonly measured bone indices in humans have been conflicting. We conducted a cross-sectional study to evaluate the association between plasma OPG and femoral neck (FN) bone density (BMD) and geometry in a large cohort of women and men. DESIGN Participants included 1379 postmenopausal women and 1165 men, aged 50-89 yr (mean, 64 yr), in the Framingham Offspring Study. Dual x-ray absorptiometry was used to evaluate FN BMD and geometry (bone width, section modulus, and cross-sectional area at the narrow neck region). Plasma OPG concentrations were measured by ELISA. Sex-specific analysis of covariance was used to calculate means and assess linear trend in BMD and geometry values across OPG quartiles, adjusted for confounders. RESULTS OPG concentrations were greater in women than men, increased with age, and were greater in smokers and those with diabetes and heart disease. Multivariable-adjusted mean FN BMD in women increased from the lowest to the highest OPG quartile (trend, P < 0.01). However, no linear trend between FN BMD and OPG was observed in men (trend, P = 0.34). Section modulus and bone width increased with OPG in men (trend, P < 0.01), whereas no association between hip geometry indices and OPG was observed in women. CONCLUSION Higher OPG concentration may indicate greater skeletal strength in women and men, possibly through reducing bone loss in women and increasing periosteal apposition in men.

Subsequent Fracture in Nursing Home Residents with a Hip Fracture: A Competing Risks Approach

OBJECTIVES: To determine the incidence and predictors of subsequent fracture in nursing home residents with a hip fracture, accounting for the competing risk of death.

Can Metacarpal Cortical Area Predict the Occurrence of Hip Fracture in Women and Men Over 3 Decades of Follow‐Up? Results From the Framingham Osteoporosis Study

The purpose of this study was to determine if a single measurement of metacarpal cortical area could predict the subsequent risk of hip fracture over a long‐term follow‐up period. Thirteen hundred eighty‐six women and 1014 men (mean age [±SD] 61 ± 8 years) underwent posteroanterior hand radiography between 1966 and 1970 as part of the Framingham Study. Measurements of cortical bone width (external width and medullary width) were made at the midpoint of the second metacarpal with a digital caliper to the nearest 0.1 mm. Hip fracture occurrence was ascertained on all survivors through December 1995. Surprisingly, in women, there was no significant increase in hip fracture according to metacarpal cortical area measurements (per SD decrease) in either age‐adjusted (hazard ratio [HR] = 1.13; 95% CI, 0.94–1.35) or multivariate‐adjusted models (HR = 1.06; 95% CI, 0.88–1.27). The same results were seen when considering only those women who were ≥65 years of age at the time of their X‐ray or when considering only the first 10 years of follow‐up. When the type of hip fracture was considered in women, after adjustment for other risk factors, there appeared to be an association between metacarpal cortical area and intertrochanteric fracture risk (HR = 1.24; 95% CI, 0.91–1.71) but not femoral neck fracture risk (HR = 0.93; 95% CI, 0.71–1.22). In men, the age‐adjusted risk of hip fracture was increased modestly per SD decrease in metacarpal cortical area (HR = 1.38; 95% CI, 1.02–1.87), and this remained true after adjustment for potential confounders. In this prospective cohort study with up to 30 years of follow‐up, metacarpal cortical area in men predicted hip fracture risk. In women, the only association between metacarpal cortical area and fracture risk was observed for intertrochanteric fractures and was not significant when adjusting for multiple potential confounders. We conclude that this peripheral measure of bone status is not a potent predictor of hip fracture over a long period of follow‐up.

Insulin-like growth factor binding proteins 4 and 5 and bone mineral density in elderly men and women

Insulin-like growth factor-1 (IGF-I) plays a central role in the maintenance of bone mass. To test whether two major IGF-I binding proteins, IGFBP-4 and IGFBP-5, are related to bone mineral density (BMD), we studied a sample of the Framingham Offspring Cohort participants (99 men and 101 women, ages 60–87). Serum levels of IGF-I, IGFBP-4, and IGFBP-5 were measured by previously validated radioimmunoassays (CVs ~10%). BMDs of the proximal femur and lumbar spine were measured using a Lunar DPX-L densitometer. In males, but not females, IGF-I and IGFBP-5 were inversely associated with age (r = 0.34 and r = -?0.28, respectively; P <0.01), while IGFBP-4 levels were positively associated with age (P <0.01). Multivariate means for BMD (adjusted for age, body mass index, height, smoking, and in women, estrogen use) were computed across quartiles of IGFBP-4 and IGFBP-5 and IGFBP-4/IGFBP-5 ratio. In women, but not men, IGFBP-5 was positively associated with femoral neck BMD (P = 0.03), however, after statistical adjustment for IGF-I, this association was no longer significant. No other associations were observed for BMD at any other site. Further study is necessary for elucidation of the gender differences in the possible influence of IGF system components on bone mass.

QCT Measures of Bone Strength at the Thoracic and Lumbar Spine: The Framingham Study

We used volumetric quantitative computed tomography (QCT) scans to evaluate volumetric bone density (vBMD), geometry, and strength in the thoracic (T8 to T10) and lumbar (L3 to L5) spine and determined how these parameters varied with age, sex, and spinal region. Participants included 690 participants of the Framingham Study, 40 to 87 years old (mean, 61 years). In both women and men, trabecular vBMD declined with age similarly for lumbar and thoracic regions, whereas cortical vBMD and integral vBMD, vertebral strength, and compressive force declined more at the lumbar spine than thoracic spine (interaction, p < 0.01). Notably, in men, cortical vBMD increased (β = 0.0004, p = 0.01), and vertebral strength did not change (β = 1.9305, p = 0.66) at the thoracic spine with age. In both women and men, vertebral cross‐sectional area increased less and the factor‐of‐risk increased more with age at the lumbar than at the thoracic region (interaction, p < 0.01). For example, in women, the factor‐of‐risk for forward flexion increased (worsened) with age 6.8‐fold more in the lumbar spine (β = 0.0157), compared with the thoracic spine (β = 0.0023). vBMD and vertebral strength declined more and the factor‐of‐risk increased more with age in women than men (interaction, p < 0.01). For instance, integral vBMD for the lumbar spine declined 36% from 40 to 75 years of age in women compared with 18% in men. There was little or no age‐related change in the forces applied to the thoracic vertebrae in either women or men. Age‐related changes were greater in the lumbar spine than in the thoracic region and greater in women than men. Whereas women lost bone density and strength at both the thoracic and lumbar spine, in men, vertebral strength declined only at the lumbar spine. Our study confirms the importance of evaluating determinants of vertebral strength in both the thoracic and lumbar spine and in both women and men to understand mechanisms underlying the structural failure of vertebral bodies with aging.