Ann V. Schwartz

Decreased Muscle Strength and Quality in Older Adults With Type 2 Diabetes: The Health, Aging, and Body Composition Study

Adequate skeletal muscle strength is essential for physical functioning and low muscle strength is a predictor of physical limitations. Older adults with diabetes have a two- to threefold increased risk of physical disability. However, muscle strength has never been investigated with regard to diabetes in a population-based study. We evaluated grip and knee extensor strength and muscle mass in 485 older adults with diabetes and 2,133 without diabetes in the Health, Aging, and Body Composition study. Older adults with diabetes had greater arm and leg muscle mass than those without diabetes because they were bigger in body size. Despite this, muscle strength was lower in men with diabetes and not higher in women with diabetes than corresponding counterparts. Muscle quality, defined as muscle strength per unit regional muscle mass, was significantly lower in men and women with diabetes than those without diabetes in both upper and lower extremities. Furthermore, longer duration of diabetes (≥6 years) and poor glycemic control (HbA1c >8.0%) were associated with even poorer muscle quality. In conclusion, diabetes is associated with lower skeletal muscle strength and quality. These characteristics may contribute to the development of physical disability in older adults with diabetes.

Central Nervous System–Active Medications and Risk for Falls in Older Women

OBJECTIVES: To determine whether current use of central nervous system (CNS)‐active medications, including benzodiazepines, antidepressants, anticonvulsants, and narcotics, increases the risk for subsequent falls.

Accelerated Loss of Skeletal Muscle Strength in Older Adults With Type 2 Diabetes The Health, Aging, and Body Composition Study

OBJECTIVE—It has been shown that adults with either long-standing type 1 or type 2 diabetes had lower skeletal muscle strength than nondiabetic adults in cross-sectional studies. The aim of the study was to investigate longitudinal changes of muscle mass and strength in community-dwelling older adults with and without type 2 diabetes. RESEARCH DESIGN AND METHODS—We examined leg and arm muscle mass and strength at baseline and 3 years later in 1,840 older adults aged 70–79 years in the Health, Aging, and Body Composition Study. Regional muscle mass was measured by dual energy X-ray absorptiometry, and muscle strength was measured using isokinetic and isometric dynamometers. RESULTS—Older adults with type 2 diabetes (n = 305) showed greater declines in the leg muscle mass (−0.29 ± 0.03 vs. −0.23 ± 0.01 kg, P < 0.05) and strength (−16.5 ± 1.2 vs. −12.4 ± 0.5 Nm, P = 0.001) compared with older adults without diabetes. Leg muscle quality, expressed as maximal strength per unit of muscle mass (Newton meters per kilogram), also declined more rapidly in older adults with diabetes (−1.6 ± 0.2 vs. −1.2 ± 0.1 Nm/kg, P < 0.05). Changes in arm muscle strength and quality were not different between those with and without diabetes. Rapid declines in leg muscle strength and quality were attenuated but remained significant after controlling for demographics, body composition, physical activity, combined chronic diseases, interleukin-6, and tumor necrosis factor-α. CONCLUSIONS—In older adults, type 2 diabetes is associated with accelerated loss of leg muscle strength and quality.

Association of BMD and FRAX score with risk of fracture in older adults with type 2 diabetes.

CONTEXT Type 2 diabetes mellitus (DM) is associated with higher bone mineral density (BMD) and paradoxically with increased fracture risk. It is not known if low BMD, central to fracture prediction in older adults, identifies fracture risk in patients with DM. OBJECTIVE To determine if femoral neck BMD T score and the World Health Organization Fracture Risk Algorithm (FRAX) score are associated with hip and nonspine fracture risk in older adults with type 2 DM. DESIGN, SETTING, AND PARTICIPANTS Data from 3 prospective observational studies with adjudicated fracture outcomes (Study of Osteoporotic Fractures [December 1998-July 2008]; Osteoporotic Fractures in Men Study [March 2000-March 2009]; and Health, Aging, and Body Composition study [April 1997-June 2007]) were analyzed in older community-dwelling adults (9449 women and 7436 men) in the United States. MAIN OUTCOME MEASURE Self-reported incident fractures, which were verified by radiology reports. RESULTS Of 770 women with DM, 84 experienced a hip fracture and 262 a nonspine fracture during a mean (SD) follow-up of 12.6 (5.3) years. Of 1199 men with DM, 32 experienced a hip fracture and 133 a nonspine fracture during a mean (SD) follow-up of 7.5 (2.0) years. Age-adjusted hazard ratios (HRs) for 1-unit decrease in femoral neck BMD T score in women with DM were 1.88 (95% confidence interval [CI], 1.43-2.48) for hip fracture and 1.52 (95% CI, 1.31-1.75) for nonspine fracture, and in men with DM were 5.71 (95% CI, 3.42-9.53) for hip fracture and 2.17 (95% CI, 1.75-2.69) for nonspine fracture. The FRAX score was also associated with fracture risk in participants with DM (HRs for 1-unit increase in FRAX hip fracture score, 1.05; 95% CI, 1.03-1.07, for women with DM and 1.16; 95% CI, 1.07-1.27, for men with DM; HRs for 1-unit increase in FRAX osteoporotic fracture score, 1.04; 95% CI, 1.02-1.05, for women with DM and 1.09; 95% CI, 1.04-1.14, for men with DM). However, for a given T score and age or for a given FRAX score, participants with DM had a higher fracture risk than those without DM. For a similar fracture risk, participants with DM had a higher T score than participants without DM. For hip fracture, the estimated mean difference in T score for women was 0.59 (95% CI, 0.31-0.87) and for men was 0.38 (95% CI, 0.09-0.66). CONCLUSIONS Among older adults with type 2 DM, femoral neck BMD T score and FRAX score were associated with hip and nonspine fracture risk; however, in these patients compared with participants without DM, the fracture risk was higher for a given T score and age or for a given FRAX score.

Central nervous system active medications and risk for fractures in older women.

BACKGROUND Use of central nervous system (CNS) active medications may increase the risk for fractures. Prior studies are limited by incomplete control of confounders. METHODS To determine whether use of CNS active medications, including benzodiazepines, antidepressants, anticonvulsants, and narcotics, increases fracture risk in elderly, community-dwelling women, we examined use of these 4 categories of medications in a cohort of 8127 older women and followed the participants prospectively for incident nonspine fractures, including hip fractures. Current use of CNS active medications was assessed by interview with verification of use from containers between 1992 and 1994 and between 1995 and 1996. Use was coded as a time-dependent variable. Incident nonspine fractures occurring after the initial medication assessment until May 31, 1999, were confirmed by radiographic reports. RESULTS During an average follow-up of 4.8 years, 1256 women (15%) experienced at least one nonspine fracture, including 288 (4%) with first hip fractures. Compared with nonusers, women taking narcotics (multivariate hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.06-1.83) and those taking antidepressants (multivariate HR, 1.25; 95% CI, 0.99-1.58) had increases in the risks for any nonspine fractures. Women taking tricyclic antidepressants and those using selective serotonin reuptake inhibitors (SSRIs) had similar fracture rates. There were no independent associations between benzodiazepine use or anticonvulsant use and risk for nonspine fracture. Women taking antidepressants compared with nonusers had a 1.7-fold increase in the risk for hip fracture (multivariate HR, 1.65; 95% CI, 1.05-2.57). We did not observe independent associations between use of any of the other 3 classes of CNS active medications and risk of hip fracture. CONCLUSIONS Community-dwelling older women taking narcotics have an increased risk for any nonspine fracture, and those taking antidepressants have a greater risk for nonspine fractures, including hip fracture. Rates of fracture were similar in women taking tricyclic antidepressants and those using SSRIs. Benzodiazepine use and anticonvulsant use were not independently associated with an increased risk of nonspine fractures, including hip fracture.

High-Resolution Peripheral Quantitative Computed Tomographic Imaging of Cortical and Trabecular Bone Microarchitecture in Patients with Type 2 Diabetes Mellitus

CONTEXT Cross-sectional epidemiological studies have found that patients with type 2 diabetes mellitus (T2DM) have a higher incidence of certain fragility fractures despite normal or elevated bone mineral density (BMD). OBJECTIVE In this study, high-resolution peripheral quantitative computed tomography was applied to characterize cortical and trabecular microarchitecture and biomechanics in the peripheral skeleton of female patients with T2DM. DESIGN AND SETTING A cross-sectional study was conducted in patients with T2DM recruited from a diabetic outpatient clinic. PARTICIPANTS Elderly female patients (age, 62.9 ± 7.7 yr) with a history of T2DM (n = 19) and age- and height-matched controls (n = 19) were recruited. OUTCOME MEASURES Subjects were imaged using high-resolution peripheral quantitative computed tomography at the distal radius and tibia. Quantitative measures of volumetric (BMD), cross-sectional geometry, trabecular and cortical microarchitecture were calculated. Additionally, compressive mechanical properties were determined by micro-finite element analysis. RESULTS Compared to the controls, the T2DM cohort had 10% higher trabecular volumetric BMD (P < 0.05) adjacent to the cortex and higher trabecular thickness in the tibia (13.8%; P < 0.05). Cortical porosity differences alone were consistent with impaired bone strength and were significant in the radius (>+50%; P < 0.05), whereas pore volume approached significance in the tibia (+118%; P = 0.1). CONCLUSION The results of this pilot investigation provide a potential explanation for the inability of standard BMD measures to explain the elevated fracture incidence in patients with T2DM. The findings suggest that T2DM may be associated with impaired resistance to bending loads due to inefficient redistribution of bone mass, characterized by loss of intracortical bone offset by an elevation in trabecular bone density.

Randomized Trial of Effect of Alendronate Continuation Versus Discontinuation in Women With Low BMD: Results From the Fracture Intervention Trial Long-Term Extension

To determine the effects of continuation versus discontinuation of alendronate on BMD and markers of bone turnover, we conducted an extension trial in which 1099 older women who received alendronate in the FIT were re‐randomized to alendronate or placebo. Compared with women who stopped alendronate, those continuing alendronate for 3 years maintained a higher BMD and greater reduction of bone turnover, showing benefit of continued treatment. However, among women who discontinued alendronate and took placebo in the extension, BMD remained higher, and reduction in bone turnover was greater than values at FIT baseline, showing persistence of alendronates effects on bone.

Diabetes Mellitus: Does it Affect Bone?

Both diabetes and fractures affect a large proportion of older adults. Recent cohort studies indicate that diabetes itself is associated with increased risk of fracture of the hip, proximal humerus, and foot. Observational studies and animal models suggest that decreased bone strength in diabetes may contribute to fracture risk but this remains a controversial issue. Type 1 diabetes is associated with modest reductions in bone mineral density (BMD) but type 2 diabetes is often characterized by elevated BMD. This paradox of higher BMD but increased fracture risk in type 2 diabetes may be explained by a combination of more frequent falls and poorer bone quality. Diabetes can impact bone through multiple pathways, some with contradictory effects, including obesity, changes in insulin levels, higher concentrations of advanced glycation end products in collagen, hypercalciuria associated with glycosuria, reduced renal function, lower insulin-like growth factor-I, microangiopathy, and inflammation. A better understanding of how diabetes metabolism and treatments affect bone would improve fracture prevention efforts in older diabetic adults.

Increased cortical porosity in type 2 diabetic postmenopausal women with fragility fractures.

The primary goal of this study was to assess peripheral bone microarchitecture and strength in postmenopausal women with type 2 diabetes with fragility fractures (DMFx) and to compare them with postmenopausal women with type 2 diabetics without fractures (DM). Secondary goals were to assess differences in nondiabetic postmenopausal women with fragility fractures (Fx) and nondiabetic postmenopausal women without fragility fractures (Co), and in DM and Co women. Eighty women (mean age 61.3 ± 5.7 years) were recruited into these four groups (DMFx, DM, Fx, and Co; n = 20 per group). Participants underwent dual‐energy X‐ray absorptiometry (DXA) and high‐resolution peripheral quantitative computed tomography (HR‐pQCT) of the ultradistal and distal radius and tibia. In the HR‐pQCT images volumetric bone mineral density and cortical and trabecular structure measures, including cortical porosity, were calculated. Bone strength was estimated using micro–finite element analysis (µFEA). Differential strength estimates were obtained with and without open cortical pores. At the ultradistal and distal tibia, DMFx had greater intracortical pore volume (+52.6%, p = 0.009; +95.4%, p = 0.020), relative porosity (+58.1%, p = 0.005; +87.9%, p = 0.011) and endocortical bone surface (+10.9%, p = 0.031; +11.5%, p = 0.019) than DM. At the distal radius DMFx had 4.7‐fold greater relative porosity (p < 0.0001) than DM. At the ultradistal radius, intracortical pore volume was significantly higher in DMFx than DM (+67.8%, p = 0.018). DMFx also displayed larger trabecular heterogeneity (ultradistal radius: +36.8%, p = 0.035), and lower total and cortical BMD (ultradistal tibia: −12.6%, p = 0.031; −6.8%, p = 0.011) than DM. DMFx exhibited significantly higher pore‐related deficits in stiffness, failure load, and cortical load fraction at the ultradistal and distal tibia, and the distal radius than DM. Comparing nondiabetic Fx and Co, we only found a nonsignificant trend with increase in pore volume (+38.9%, p = 0.060) at the ultradistal radius. The results of our study suggest that severe deficits in cortical bone quality are responsible for fragility fractures in postmenopausal diabetic women.

Type 2 diabetes and bone.

There is a growing body of research showing that diabetes is an independent risk factor for fracture. Type 2 diabetes (T2D), which predominates in older individuals and is increasing globally as a consequence of the obesity epidemic, is associated with normal or even increased dual‐energy x‐ray absorptiometry (DXA)‐derived areal bone mineral density (BMD). Therefore, the paradoxical increase in fracture risk has led to the hypothesis that there are diabetes‐associated alterations in material and structural properties. An overly glycated collagen matrix, confounded by a low turnover state, in the setting of subtle cortical abnormalities, may lead to compromised biomechanical competence. In current clinical practice, because BMD is central to fracture prediction, a consequence of this paradox is a lack of suitable methods, including FRAX, to predict fracture risk in older adults with T2D. The option of adding diabetes to the FRAX algorithm is appealing but requires additional data from large population‐based cohorts. The need for improved methods for identification of fracture in older adults with T2D is an important priority for osteoporosis research.