Journal of Bone and Mineral Research最新文献

Type 2 diabetes mellitus (T2DM) is common in patients with chronic kidney disease (CKD). Both conditions associate with an increased fracture risk, with proposed etiology including impaired bone quantity and quality. This cross-sectional study examined the bone phenotype in patients with T2DM and kidney failure and explored the role of glycemic control on the bone phenotype. To do so laboratory parameters of mineral metabolism (including sclerostin) and bone turnover markers (BTM) (bone-specific alkaline phosphatase (BALP), trimeric pro-collagen type I N-terminal propeptide (intact PINP) and tartrate-resistant acid phosphatase isoform 5b (TRACP5b)) were assessed in 647 patients with kidney failure, of which 102 had T2DM (median hemoglobin A1c (HbA1c) of 6.2%), at time of kidney transplantation. Patients with type 1 DM were excluded. Bone mineral density (BMD, n = 555) by densitometry, and bone histomorphometry (n = 188) were available for subsets, and correlations between HbA1c and both BTM and BMD were examined. This study found that intact PINP was lower (68 vs. 82 μg/L, p = .03) while sclerostin was higher (2.1 vs. 1.8 ng/mL, p = .04) in T2DM versus non-T2DM in unadjusted analysis. BMD at the lumbar spine (Z-score - 0.066 vs. -0.760, p < .001) and femoral neck (Z-score - 0.680 vs. -0.965, p = .04) were higher in T2DM, and T2DM was in multivariable regression analysis identified as a significant determinant of lumbar spine BMD, independent of age, sex, and BMI. Bone histomorphometric parameters did not differ between groups. A correlation between HbA1c and BTM and BMD was present, but only in non-T2DM (BALP (ρ = -0.12, p = .007), intact PINP (ρ = 0.14, p = .002), TRACP5b (ρ = -0.13, p = .003), BMD at lumbar spine (ρ = 0.12, p = .008), femoral neck (ρ = 0.11, p = .02), and total hip (ρ = 0.17, p < .001)). In conclusion, patients with kidney failure and T2DM have preserved BMD compared to patients without diabetes. Our findings suggest a role for hyperglycemia as a determinant of the bone phenotype.

The current version of FRAX® does not consider prior falls as a primary input variable. Limited data suggest that greater FRAX-derived fracture probability is associated with incident falls at least in elderly men. Our aim was to examine the association of FRAX-derived fracture probability with the risk for subsequent fall-associated hospitalizations. We identified individuals aged 40 years or older at the time of baseline DXA with FRAX-derived major osteoporotic fracture (MOF) probability assessed through the Manitoba BMD Program. We used linkage with population-based data to identify subsequent hospitalization that included a fall diagnosis code. Sensitivity analyses examined fall-associated hospitalizations unrelated to a concurrent fracture (diagnosed within 30 days). Cox regression was used to estimate hazard ratios (HR) for time to fall-associated hospitalization according to MOF probability without and with BMD (per SD increase and also for individual variables in the FRAX tool). The study comprised 88,684 individuals, mean age 64.6 years, 89.5% female. During mean 8.6 years observation (total 759,963 person-years), 9715 (11.0%) individuals experienced a fall-associated hospitalization; of these, 3363 (3.8%) were unrelated to concurrent fracture. Every SD increase in MOF fracture probability was strongly associated with fall-associated hospitalization (without BMD HR 2.47, 95%CI 2.41-2.52; with BMD HR 2.48, 95%CI 2.43-2.53). No significant interaction was seen between fracture probability and follow-up time (p=0.516). Findings were similar when restricted to individuals with falls unrelated to concurrent fracture, when adjusted for previous fall-associated hospitalization (last 3 years) or self-reported fall (last 12 months), when restricted to individuals without previous falls, and for FRAX-derived hip fracture probability. All FRAX variables except for parental hip fracture showed a positive relationship with fall-associated hospitalization. In conclusion, FRAX-derived fracture probability is strongly associated with risk for future fall-associated hospitalization, including falls unrelated to concurrent fracture.

Although preclinical studies suggest that omega-3 fatty acids may benefit skeletal health, there are few randomized controlled trials investigating effects of supplemental omega-3 on bone outcomes. This VITamin D and OmegA-3 TriaL (VITAL) ancillary study investigated effects of marine omega-3 (1 g/d; EPA + DHA in a 1.2:1 ratio) vs. placebo supplements on fracture risk and bone density/structure. VITAL is a 2x2 factorial randomized placebo-controlled trial that studied effects of supplemental marine omega-3 fatty acids and/or vitamin D3 vs. placebo on cancer and cardiovascular events. The intervention took place from November 2011 through December 2017; median follow-up was 5.3 yr. The study included 25 871 U.S. men (aged ≥50) and women (aged ≥55) without baseline cancer or cardiovascular disease, not selected for low bone density or fracture history. Primary outcomes were adjudicated incident total, nonvertebral, and hip fractures in the overall cohort. In a subcohort of 771 individuals, we measured 2-yr changes in areal bone mineral density (aBMD) by dual X-ray absorptiometry, and volumetric bone mineral density (vBMD), cortical thickness, and bone strength indices at the radius and tibia by peripheral quantitative computed tomography. Supplemental omega-3 vs. placebo had no effect on total (HR, 1.02; 95% CI, 0.92-1.13; p = .73), nonvertebral (HR, 1.01; 95% CI, 0.91-1.12; p = .80), or hip fractures (HR, 0.89; 95% CI, 0.61-1.30; p = .55). In the subcohort, omega-3 supplementation resulted in a small increase in whole body aBMD (+0.03% vs. -0.41%, p = .006) and no effect on aBMD at the spine or hip, or vBMD or bone strength indices at the radius or tibia. No serious adverse effects were observed. Supplementation with marine omega-3 fatty acids did not reduce incident fracture risk. It led to a small increase in whole body aBMD but had no other effects on BMD or bone strength measures compared to placebo in generally healthy midlife and older adults.

The anti-fracture efficacy of most osteoporosis drugs is assessed in trials of up to three years duration. However, treatment of osteoporosis is required long-term, so it is important to know whether effectiveness of treatment changes over time. To-date, this information has only been available from open extensions of the treatment groups from clinical trials. Such data are subject to selective loss of frailer patients from the cohort, and no placebo comparator group is available to permit reliable measurement of anti-fracture efficacy. The 6-year Auckland zoledronate RCT administered zoledronate or placebo every 18 months to 2000 osteopenic women aged >65 years. It is longer than most osteoporosis trials, and only 3.6% of participants withdrew or were lost to follow-up. Therefore, anti-fracture efficacy can be validly compared between the first and second halves of this study. There were 178 non-vertebral fractures in the placebo group and 108 in the zoledronate group (excluding fractures of the hands, feet and face). Fracture rates per 1000 women-years in the placebo group were 28 (95%CI 23, 35) and 32 (26, 40) in years 1-3 and years 4-6, respectively. In the zoledronate group, fracture rates were 23 (18, 30) and 13 (9, 18) per 1000 women-years in the first and second halves of the study. The rate ratios for non-vertebral fractures were 0.83 (0.60, 1.14) in years 1-3, and 0.40 (0.27, 0.58) in years 4-6 (between-period comparison, P<0.05). Rate ratios for total fragility fractures, which include vertebral fractures also, showed a similar pattern: years 1-3, 0.76 (0.56, 1.02); years 4-6, 0.39 (0.29, 0.53). These findings suggest that the efficacy for non-vertebral fracture prevention of anti-resorptive drugs has been underestimated because of the short-term evaluation of their effects. Further, it indicates that longer term treatment with these drugs may yield greater benefit to patients.