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Background: Interspinous spacer/implants like the Device for Intervertebral Assisted Motion (DIAM™) are controversially yet commonly used in the surgical treatment of lumbar degenerative pathologies. Criticism is based on ill-defined indications, lack of superiority over decompression, and a poorly understood mechanical effect. Yet, continued use by surgeons implies their perceived clinical merit. We examined radiographic spinal alignment for 12 months, and pain and function for 24 months, after DIAM-augmented surgery to improve the understanding of the mechanical effect relating to clinical outcomes in patients. Methods: We undertook a single-surgeon prospective, longitudinal study of 40 patients (20 F, 20 M) who received DIAM-augmented surgery in treatment of their symptomatic lumbar degenerative condition. Outcomes measured included sagittal spinal alignment (lumbar lordosis, sacral inclination, primary (PDA), supradjacent (SDA) disc angles, and regional sagittal balance (RSB; standing lateral radiographs), and back and leg pain (visual analogue scale; VAS) and function (Oswestry Disability Index; ODI). Responders were identified as those with clinically meaningful improvement to pain (>20%) and function (>15%) at 24 months postoperatively; features of sagittal spinal alignment between responders and non-responders were examined. Results: Sagittal alignment was unchanged at 12 months. At 6 weeks postoperatively, PDA (mean (SD)) reduced by 2.2° (4.0°; p < 0.01) and more-so in back pain non-responders (3.8° (3.2°)) than responders (0.7° (4.4°); p < 0.05). Positive preoperative RSB in responders (26.7Rmm (42.3Rmm); Rmm is a system-relative measure) decreased at 6 weeks (by 3.1Rmm (9.1Rmm)). Non-responders had a negative RSB preoperatively (−1.0Rmm (32.0Rmm)) and increased at 6 weeks (11.2Rmm (15.5Rmm); p < 0.05). Clinically meaningful improvement for the whole cohort for back pain and function were observed to 24 months (back pain: 25.0% (28.0); function: 15.4% (17.

Osteoporosis is a complex disorder and commonly leads to fractures in elderly persons. Genome-wide association studies (GWAS) have become an unbiased approach to identify variations in the genome that potentially affect health. However, the genetic variants identified so far only explain a small proportion of the heritability for complex traits. Due to the modest genetic effect size and inadequate power, true association signals may not be revealed based on a stringent genome-wide significance threshold. Here, we take advantage of SNP and transcript arrays and integrate GWAS and expression signature profiling relevant to the skeletal system in cellular and animal models to prioritize the discovery of novel candidate genes for osteoporosis-related traits, including bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN), as well as geometric indices of the hip (femoral neck-shaft angle, NSA; femoral neck length, NL; and narrow-neck width, NW). A two-stage meta-analysis of GWAS from 7,633 Caucasian women and 3,657 men, revealed three novel loci associated with osteoporosis-related traits, including chromosome 1p13.2 (RAP1A, p = 3.6 x 10(-8)), 2q11.2 (TBC1D8), and 18q11.2 (OSBPL1A), and confirmed a previously reported region near TNFRSF11B/OPG gene. We also prioritized 16 suggestive genome-wide significant candidate genes based on their potential involvement in skeletal metabolism. Among them, 3 candidate genes were associated with BMD in women. Notably, 2 out of these 3 genes (GPR177, p = 2.6 x 10(-13); SOX6, p = 6.4 x 10(-10)) associated with BMD in women have been successfully replicated in a large-scale meta-analysis of BMD, but none of the non-prioritized candidates (associated with BMD) did. Our results support the concept of our prioritization strategy. In the absence of direct biological support for identified genes, we highlighted the efficiency of subsequent functional characterization using publicly available expression profiling relevant t

A population-based study on 1008 postmenopausal women identified that the 24% of women achieving high levels of PA and CI had 3.4–4.4% higher femoral bone strength in axial compression and 1.7–5.2% in bending than those achieving low levels, indicating that lifestyle factors influence bone strength in the proximal femur. Introduction: Extensive research has shown that increased physical activity (PA) and calcium intake (CI) decrease the rate of bone loss; however, there is little research on how these lifestyle variables affect bone geometry. This study was designed to investigate the effects of modifiable lifestyle variables, habitual PA and dietary CI, on femoral geometry in older women. Materials and Methods: Femoral geometry, habitual PA, and dietary CI were measured in a population-based sample of 1008 women (median age ± interquartile range, 75 ± 4years) enrolled in a randomized controlled trial (RCT) of calcium supplementation. Baseline PA and CI were assessed by validated questionnaires, and 1-year DXA scans (Hologic 4500A) were analyzed using the hip structural analysis technique. Section modulus (Z), an index of bending strength, cross-sectional area (CSA), an index of axial compression strength, subperiosteal width (SPW), and centroid position, the position of the center of mass, were measured at the femoral neck (NN), intertrochanter (IT), and femoral shaft (FS) sites. These data were divided into tertiles of PA and CI, and the results were compared using analysis of covariance (ANCOVA), with corrections for age, height, weight, and treatment (calcium/placebo). Results and Conclusions: PA showed a significant dose–response effect on CSA all hip sites (p < 0.03) and Z at the narrow neck and intertrochanter sites (p < 0.02). For CI, there was a dose–response effect for centroid position at the intertrochanter (p = 0.03). These effects were additive, such that the women (n = 240) with PA in excess of 65.5 kcal/day and CI in excess of 1039 mg/day had signifi