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30. Retrospective Study of Serum Sclerostin Measurements in Bed Rest Subjects

Author

Spatz, J. M, Fields, E. E, Yu, E. W, Divieti, Pajevic P, Bouxsein, M. L, Sibonga, M. L, Zwart, S. R, and Smith, S. M

Subjects
Aerospace Medicine
Abstract

Animal models and human studies suggest that osteocytes regulate the skeleton s response to mechanical unloading at the cellular level in part by an increase in sclerostin, an inhibitor of the anabolic Wnt pathway. However, few studies have reported changes in serum sclerostin in humans exposed to reduced mechanical loading. Thus, we determined changes in serum sclerostin and bone turnover markers in healthy adult men who participated in a controlled bed rest study. Seven healthy adult men (31 +/- 3 yrs old) underwent 90-day six-degree head down tilt bed rest at the University of Texas Medical Branch in Galveston's Institute for Translational Sciences - Clinical Research Center (ITS-CRC). Serum sclerostin, PTH, serum markers of bone turnover (bone specific alkaline phosphatase, RANKL/OPG, and osteocalcin), urinary calcium and phosphorus excretion, and 24 hour pooled urinary markers of bone resorption (NTX, DPD, PYD) were evaluated pre-bed rest (BL), bed rest day 28 (BR-28), bed rest day 60 (BR-60), and bed rest day 90 (BR-90). In addition, bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry (DXA) at BL, BR-60, and post bed rest day 5 (BR+5). Data are reported as mean +/- standard deviation. We used repeated measures ANOVA to compare baseline values to BR-28, BR-60, and BR-90. RESULTS Consistent with prior reports, BMD declined significantly (1-2% per month) at weight-bearing skeletal sites (spine, hip, femur neck, and calcaneus). Serum sclerostin levels were elevated above BL at BR-28 (+29% +/- 20%, p = 0.003), BR-60 (+42% +/- 31%, p < 0.001), and BR-90 (22% +/- 21%, p = 0.07). Serum PTH levels were reduced at BR-28 (-17% +/- 16%, p = 0.02), BR-60 (-24% +/- 14%, p = 0.03), and returned to baseline at BR-90 (-21% +/- 21%, p = 0.14). Serum bone turnover markers did not change, however urinary bone resorption markers and calcium were significantly elevated following bed rest (p < 0.01). CONCLUSION We observed an increase of serum sclerostin associated with decreased serum PTH and elevated bone resorption markers in otherwise healthy men subjected to long-term immobilization.

Published
2011

32. Data Mining Activity for Bone Discipline: Calculating a Factor of Risk for Hip Fracture in Long-Duration Astronauts

Author

Ellman, R, Sibonga, J. D, and Bouxsein, M. L

Subjects
Aerospace Medicine
Abstract

The factor-of-risk (Phi), defined as the ratio of applied load to bone strength, is a biomechanical approach to hip fracture risk assessment that may be used to identify subjects who are at increased risk for fracture. The purpose of this project was to calculate the factor of risk in long duration astronauts after return from a mission on the International Space Station (ISS), which is typically 6 months in duration. The load applied to the hip was calculated for a sideways fall from standing height based on the individual height and weight of the astronauts. The soft tissue thickness overlying the greater trochanter was measured from the DXA whole body scans and used to estimate attenuation of the impact force provided by soft tissues overlying the hip. Femoral strength was estimated from femoral areal bone mineral density (aBMD) measurements by dual-energy x-ray absorptiometry (DXA), which were performed between 5-32 days of landing. All long-duration NASA astronauts from Expedition 1 to 18 were included in this study, where repeat flyers were treated as separate subjects. Male astronauts (n=20) had a significantly higher factor of risk for hip fracture Phi than females (n=5), with preflight values of 0.83+/-0.11 and 0.36+/-0.07, respectively, but there was no significant difference between preflight and postflight Phi (Figure 1). Femoral aBMD measurements were not found to be significantly different between men and women. Three men and no women exceeded the theoretical fracture threshold of Phi=1 immediately postflight, indicating that they would likely suffer a hip fracture if they were to experience a sideways fall with impact to the greater trochanter. These data suggest that male astronauts may be at greater risk for hip fracture than women following spaceflight, primarily due to relatively less soft tissue thickness and subsequently greater impact force.

Published
2010

34. Perspectives on the non-invasive evaluation of femoral strength in the assessment of hip fracture risk

Author

Bouxsein, M. L., Zysset, P., Glüer, C. C., McClung, M., Biver, Emmanuel, Pierroz, D.D., Ferrari, Serge Livio, and IOF Working Group on Hip Bone Strength as a Therapeutic Target

Subjects
0301 basic medicine, musculoskeletal diseases, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Osteoporosis, Finite Element Analysis, 030209 endocrinology & metabolism, Bone strength, Bone tissue, Hip fracture, 03 medical and health sciences, 0302 clinical medicine, Absorptiometry, Photon, Bone Density, medicine, Humans, Femur, Pelvic Bones, Aged, Orthodontics, Bone mineral, ddc:616, Surrogate endpoint, business.industry, Hip Fractures, Finite element analysis (FEA), medicine.disease, musculoskeletal system, medicine.anatomical_structure, Hip bone, Case-Control Studies, Orthopedic surgery, Fracture (geology), Female, 030101 anatomy & morphology, business, Bone mineral density (BMD)
Abstract

We reviewed the experimental and clinical evidence that hip bone strength estimated by BMD and/or finite element analysis (FEA) reflects the actual strength of the proximal femur and is associated with hip fracture risk and its changes upon treatment. The risk of hip fractures increases exponentially with age due to a progressive loss of bone mass, deterioration of bone structure, and increased incidence of falls. Areal bone mineral density (aBMD), measured by dual-energy X-ray absorptiometry (DXA), is the most used surrogate marker of bone strength. However, age-related declines in bone strength exceed those of aBMD, and the majority of fractures occur in those who are not identified as osteoporotic by BMD testing. With hip fracture incidence increasing worldwide, the development of accurate methods to estimate bone strength in vivo would be very useful to predict the risk of hip fracture and to monitor the effects of osteoporosis therapies. We reviewed experimental and clinical evidence regarding the association between aBMD and/orCT-finite element analysis (FEA) estimated femoral strength and hip fracture risk as well as their changes with treatment. Femoral aBMD and bone strength estimates by CT-FEA explain a large proportion of femoral strength ex vivo and predict hip fracture risk in vivo. Changes in femoral aBMD are strongly associated with anti-fracture efficacy of osteoporosis treatments, though comparable data for FEA are currently not available. Hip aBMD and estimated femoral strength are good predictors of fracture risk and could potentially be used as surrogate endpoints for fracture in clinical trials. Further improvements of FEA may be achieved by incorporating trabecular orientations, enhanced cortical modeling, effects of aging on bone tissue ductility, and multiple sideway fall loading conditions.

Published
2019

43. Prediction of incident vertebral fracture using CT-based finite element analysis

Author

Allaire, B. T., primary, Lu, D., additional, Johannesdottir, F., additional, Kopperdahl, D., additional, Keaveny, T. M., additional, Jarraya, M., additional, Guermazi, A., additional, Bredella, M. A., additional, Samelson, E. J., additional, Kiel, D. P., additional, Anderson, D. E., additional, Demissie, S., additional, and Bouxsein, M. L., additional

Published
2018
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45. The associations between QCT-based vertebral bone measurements and prevalent vertebral fractures depend on the spinal locations of both bone measurement and fracture

Author

Harvard University--MIT Division of Health Sciences and Technology, Bruno, Alexander Gregory, Demissie, S., Anderson, D. E., Allaire, B. T., Kopperdahl, D. L., Keaveny, T. M., Kiel, D. P., Bouxsein, M. L., Harvard University--MIT Division of Health Sciences and Technology, Bruno, Alexander Gregory, Demissie, S., Anderson, D. E., Allaire, B. T., Kopperdahl, D. L., Keaveny, T. M., Kiel, D. P., and Bouxsein, M. L.

Abstract

Summary We examined how spinal location affects the relationships between quantitative computed tomography (QCT)-based bone measurements and prevalent vertebral fractures. Upper spine (T4–T10) fractures appear to be more strongly related to bone measures than lower spine (T11–L4) fractures, while lower spine measurements are at least as strongly related to fractures as upper spine measurements. Introduction Vertebral fracture (VF), a common injury in older adults, is most prevalent in the mid-thoracic (T7–T8) and thoracolumbar (T12–L1) areas of the spine. However, measurements of bone mineral density (BMD) are typically made in the lumbar spine. It is not clear how the associations between bone measurements and VFs are affected by the spinal locations of both bone measurements and VF. Methods A community-based case–control study includes 40 cases with moderate or severe prevalent VF and 80 age- and sex-matched controls. Measures of vertebral BMD, strength (estimated by finite element analysis), and factor of risk (load:strength ratio) were determined based on QCT scans at the L3 and T10 vertebrae. Associations were determined between bone measures and prevalent VF occurring at any location, in the upper spine (T4–T10), or in the lower spine (T11–L4). Results Prevalent VF at any location was significantly associated with bone measures, with odds ratios (ORs) generally higher for measurements made at L3 (ORs = 1.9–3.9) than at T10 (ORs = 1.5–2.4). Upper spine fracture was associated with these measures at both T10 and L3 (ORs = 1.9–8.2), while lower spine fracture was less strongly associated (ORs = 1.0–2.4) and only reached significance for volumetric BMD measures at L3. Conclusions Closer proximity between the locations of bone measures and prevalent VF does not strengthen associations between bone measures and fracture. Furthermore, VF etiology may vary by region, with VFs in the upper spine more strongly related to skeletal fragility., National Institutes of Health (U.S.) (Grants R01AR053986, R01AR/AG041398, T32AG023480, and F31AG041629), National Heart, Lung, and Blood Institute. Framingham Heart Study (NIH/NHLBI Contract N01-HC-25195)

Published
2016

46. Operator variability in scan positioning is a major component of HR-pQCT precision error and is reduced by standardized training

Author

Bonaretti, S., primary, Vilayphiou, N., additional, Chan, C. M., additional, Yu, A., additional, Nishiyama, K., additional, Liu, D., additional, Boutroy, S., additional, Ghasem-Zadeh, A., additional, Boyd, S. K., additional, Chapurlat, R., additional, McKay, H., additional, Shane, E., additional, Bouxsein, M. L., additional, Black, D. M., additional, Majumdar, S., additional, Orwoll, E. S., additional, Lang, T. F., additional, Khosla, S., additional, and Burghardt, A. J., additional

Published
2016
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48. Characterization of trabecular bone microstructure in premenopausal women with distal radius fractures.

Author

Rozental, T. D., Johannesdottir, F., Kempland, K. C., and Bouxsein, M. L.

Subjects
BEHAVIOR modification, COMPUTED tomography, BONE fractures, HEALTH behavior, RADIAL bone, RADIUS bone injuries, TIBIA, PERIMENOPAUSE, BONE density, PHOTON absorptiometry, CANCELLOUS bone, ODDS ratio
Abstract

Summary: Individual trabecular segmentation was utilized to identify differences in trabecular bone structure in premenopausal women with wrist fractures and non-fracture controls. Fracture subjects had reduced trabecular plate volume, number, thickness, and connectivity. Identifying altered trabecular microarchitecture in young women offers opportunities for counseling and lifestyle modifications to reduce fracture risk.Introduction: Premenopausal women with distal radius fractures (DRF) have worse trabecular bone microarchitecture than non-fracture controls (CONT), yet the characteristics of their trabecular bone structure are unknown.Methods: Premenopausal women with DRF (n = 40) and CONT (n = 80) were recruited. Primary outcome variables included trabecular structure at the distal radius and tibia, assessed by volumetric decomposition of individual trabecular plates and rods from high-resolution peripheral quantitative CT images. Trabecular morphology included plate and rod number, volume, thickness, and connectivity. Areal bone mineral density (aBMD) of the femoral neck (FN aBMD), and ultradistal radius (UDR aBMD) were measured by DXA.Results: Trabecular morphology differed between DRF and CONT at the radius and tibia (OR per SD decline 1.58–2.7). At the radius, associations remained significant when adjusting for age and FN aBMD (ORs = 1.76–3.26) and age and UDR aBMD (ORs = 1.72–3.97). Plate volume fraction, number and axially aligned trabeculae remained associated with DRF after adjustment for trabecular density (ORs = 2.55–2.85). Area under the curve (AUC) for discriminating DRF was 0.74 for the proportion of axially aligned trabeculae, compared with 0.60 for FN aBMD, 0.65 for UDR aBMD, and 0.69 for trabecular density. Plate number, plate-plate junction, and axial bone volume fraction remained associated with DRF at the tibia (ORs = 2.14–2.77) after adjusting for age, FN aBMD, or UDR aBMD. AUCP.P.Junc.D was 0.72 versus 0.61 for FNaBMD, 0.66 for UDRaBMD, and 0.70 for trabecular density.Conclusion: Premenopausal women with DRF have lower trabecular plate volume, number, thickness, and connectivity than CONT. Identification of young women with altered microarchitecture offers opportunities for lifestyle modifications to reduce fracture risk. [ABSTRACT FROM AUTHOR]

Published
2018
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