Estimated Bone Strength Research Articles

Benefits and Risks of Testosterone Treatment in Men with Age-Related Decline in Testosterone.

The substantial increase in life expectancy of men has focused growing attention on quality-of-life issues associated with reproductive aging. Serum total and free testosterone levels in men, after reaching a peak in the second and third decade of life, decline gradually with advancing age. The trajectory of age-related decline is affected by comorbid conditions, adiposity, medications, and genetic factors. Testosterone treatment of older men with low testosterone levels improves overall sexual activity, sexual desire, and erectile function; improves areal and volumetric bone density, as well as estimated bone strength in the spine and the hip; corrects unexplained anemia of aging; increases skeletal muscle mass, strength and power, self-reported mobility, and some measures of physical function; and modestly improves depressive symptoms. The long-term effects of testosterone on major cardiovascular events and prostate cancer risk remain unclear. The Endocrine Society recommends against testosterone therapy of all older men with low testosterone levels but suggests consideration of treatment on an individualized basis in men who have consistently low testosterone levels and symptoms or conditions suggestive of testosterone deficiency.

Subject-specific FE models of the human femur predict fracture path and bone strength under single-leg-stance loading

Hip fractures are a major health problem with high socio-economic costs. Subject-specific finite element (FE) models have been suggested to improve the fracture risk assessment, as compared to clinical tools based on areal bone mineral density, by adding an estimate of bone strength. Typically, such FE models are limited to estimate bone strength and possibly the fracture onset, but do not model the fracture process itself. The aim of this study was to use a discrete damage approach to simulate the full fracture process in subject-specific femur models under stance loading conditions. A framework based on the partition of unity finite element method (PUFEM), also known as XFEM, was used. An existing PUFEM framework previously used on a homogeneous generic femur model was extended to include a heterogeneous material description together with a strain-based criterion for crack initiation. The model was tested on two femurs, previously mechanically tested in vitro. Our results illustrate the importance of implementing a subject-specific material distribution to capture the experimental fracture pattern under stance loading. Our models accurately predicted the fracture pattern and bone strength (1% and 5% error) in both investigated femurs. This is the first study to simulate complete fracture paths in subject-specific FE femur models and it demonstrated how discrete damage models can provide a more complete picture of fracture risk by considering both bone strength and fracture toughness in a subject-specific fashion.

Hip Structural Analysis Reveals Impaired Hip Geometry in Girls With Type 1 Diabetes.

Among patients with type 1 diabetes (T1D), the risk of hip fracture is up to 6-fold greater than that of the general population. However, the cause of this skeletal fragility remains poorly understood. To assess differences in hip geometry and imaging-based estimates of bone strength between youth with and without T1D using dual-energy x-ray absorptiometry (DXA)-based hip structural analysis. Cross-sectional comparison. Girls ages 10 to 16 years, including n = 62 with T1D and n = 61 controls. The groups had similar age, bone age, pubertal stage, height, lean mass, and physical activity. Bone mineral density at the femoral neck and total hip did not differ in univariate comparisons but was lower at the femoral neck in T1D after adjusting for bone age, height, and lean mass. Subjects with T1D had significantly lower cross-sectional area, cross-sectional moment of inertia, section modulus, and cortical thickness at the narrow neck, with deficits of 5.7% to 10.3%. Cross-sectional area was also lower at the intertrochanteric region in girls with T1D. Among those T1D subjects with HbA1c greater than the cohort median of 8.5%, deficits in hip geometry and strength estimates were more pronounced. DXA-based hip structural analysis revealed that girls with T1D have unfavorable geometry and lower estimates of bone strength at the hip, which may contribute to skeletal fragility and excess hip fracture risk in adulthood. Higher average glycemia may exacerbate effects of T1D on hip geometry.

Effects of Combination Denosumab and High-Dose Teriparatide Administration on Bone Microarchitecture and Estimated Strength: The DATA-HD HR-pQCT Study.

In postmenopausal women at high risk of fracture, we previously reported that combined denosumab and high-dose (HD; 40 μg) teriparatide increased spine and hip bone mineral density (BMD) more than combination with standard-dose teriparatide (SD; 20 μg). To assess the effects of these combinations on bone microarchitecture and estimated bone strength, we performed high-resolution peripheral quantitative computed tomography (HR-pQCT) at the distal radius and distal tibia in these women, who were randomized to receive either teriparatide 20 μg (n = 39) or 40 μg (n = 37) during months 0 to 9 overlapped with denosumab 60 mg s.c. given at months 3 and 9, for a 15-month study duration. The 69 women who completed at least one study visit after baseline are included in this analysis. Over 15 months, increases in total BMD were higher in the HD-group than the SD-group at the distal tibia (5.3% versus 3.4%, p = 0.01) with a similar trend at the distal radius (2.6% versus 1.0%, p = 0.06). At 15 months, cortical porosity remained similar to baseline, with absolute differences of -0.1% and -0.7% at the distal tibia and -0.4% and -0.1% at the distal radius in the HD-group and SD-group, respectively; p = NS for all comparisons. Tibial cortical tissue mineral density increased similarly in both treatment groups (1.3% [p < 0.0001 versus baseline] and 1.5% [p < 0.0001 versus baseline] in the HD-group and SD-group, respectively; p = 0.75 for overall group difference). Improvements in trabecular microarchitecture at the distal tibia and estimated strength by micro-finite element analysis at both sites were numerically greater in the HD-group compared with SD-group but not significantly so. Together, these findings suggest that short-term treatment combining denosumab with either high- or standard-dose teriparatide improves HR-pQCT measures of bone density, microstructure, and estimated strength, with greater gains in total bone density observed in the HD-group, which may be of benefit in postmenopausal women with severe osteoporosis. © 2020 American Society for Bone and Mineral Research (ASBMR).

In vivo repeatability of homogenized finite element analysis based on multiple HR-pQCT sections for assessment of distal radius and tibia strength.

Micro finite element analysis (μFE) is a widely applied tool in biomedical research for assessing in vivo mechanical properties of bone at measurement sites, including the ultra-distal radius and tibia. A finite element approach (hFE) based on homogenized constitutive models for trabecular bone offers an attractive alternative for clinical use, as it is computationally less expensive than traditional μFE. The respective patient-specific models for in vivo bone strength estimation are usually based on standard clinical high-resolution peripheral quantitative CT (HR-pQCT) measurements. They include a scan region of roughly 10mm in height and are referred to as single-sections. It has been shown, that these small peripheral bone sections don't reliably cover the fracture line in Colles' fractures and therefore the weakest region at the radius. Recently introduced multiple section (multiple adjacent single-sections) measurements might improve the evaluation of bone strength, but little is known about the repeatability of hFE estimations in general, and especially for multiple section measurement protocols. Accordingly, the aim of the present work is to quantify repeatability of clinical in vivo bone strength measurement by hFE on multiple section HR-pQCT reconstructions at the distal radius and tibia. Nineteen healthy Swiss women (43.6y±17.8y) and twenty men (48.2y±19.4y) were examined with HR-pQCT at 61μm isotropic voxel resolution. Each subject was first scanned three times using a double-section (336 slices) at the distal radius and then three times using a triple-section (504 slices) at the distal tibia. The multiple section HR-pQCT reconstructions were graded for motion artefacts and non-linear hFE models (radius and tibia) and linear μFE models (only radius) were generated for estimation of stiffness and ultimate load. Then in vivo repeatability errors were computed in terms of root mean square coefficients of variation (CV). In vivo repeatability errors of non-linear hFE stiffness (S) and ultimate load (F) were significantly higher at the radius (S: 2.71% and F: 2.97%) compared to the tibia (S: 1.21%, F: 1.45%). Multiple section linear μFE at the radius resulted in substantially higher repeatability errors (S: 5.38% and F: 10.80%) compared to hFE. Repeatability errors of hFE outcomes based on multiple section measurements at the distal radius and tibia were generally lower compared to respective reported single-section μFE repeatability errors. Therefore, hFE is an attractive alternative to today's gold standard of μFE models and should especially be encouraged when analyzing multiple section measurements.

Adverse Effects of High-Dose Vitamin D Supplementation on Volumetric Bone Density Are Greater in Females than Males

Three years of high-dose vitamin D supplementation (400 IU, 4000 IU, 10,000 IU) in healthy vitamin D-sufficient individuals aged 55 to 70 years (serum 25(OH)D 30-125 nmol/L at baseline), resulted in a negative dose-response relationship for bone density and strength. This study examined whether response differed between males and females. A total of 311 participants (53% male) were randomized to 400 IU (male = 61, female = 48), 4000 IU (male = 51, female = 49), or 10,000 IU (male = 53, female = 49) daily vitamin D3 . Participants were scanned with high-resolution peripheral quantitative computed tomography (HR-pQCT) to measure total volumetric BMD (TtBMD) at baseline, 6, 12, 24, and 36 months. Finite element analysis estimated bone strength. Balance, physical function, and clinical biochemistry parameters were also assessed. Constrained linear mixed effects models determined time-by-treatment group-by-sex interactions. Baseline, 3-month, and 3-year levels of 25(OH)D were 76.3, 76.7, and 77.4 nmol/L (400 IU); 81.3, 115.3, and 132.2 (4000 IU); and 78.4, 188.0, and 144.4 (10,000 IU), respectively. There were significant time-by-treatment group-by-sex interactions for TtBMD at the radius (p = .002) and tibia (p = .005). Treatment with 4000 IU or 10,000 IU compared to 400 IU resulted in TtBMD losses in females, but this was not observed with males. After 3 years, females lost 1.8% (400 IU), 3.8% (4000 IU), and 5.5% (10,000 IU), whereas males lost 0.9% (400 IU), 1.3% (4000 IU), and 1.9% (10,000 IU) at the radius. At the tibia, losses in TtBMD were smaller, but followed a similar trend. There were no significant bone strength interactions. Vitamin D supplementation with 4000 IU or 10,000 IU, compared with 400 IU daily, resulted in greater losses of TtBMD over 3 years in healthy vitamin D-sufficient females, but not males. These results are clinically relevant, because vitamin D supplementation is widely administered to postmenopausal females for osteoporosis prevention. Our findings do not support a benefit of high-dose vitamin D supplementation for bone health, and raise the possibility of harm for females. © 2020 American Society for Bone and Mineral Research (ASBMR).

Lower estimated bone strength and impaired bone microarchitecture in children with type 1 diabetes

IntroductionPatients with type 1 diabetes has an increased risk of fracture. We wished to evaluate estimated bone strength in children and adolescents with type 1 diabetes and assess peripheral bone...

Restoration of euthyroidism in women with Hashimoto's thyroiditis changes bone microarchitecture but not estimated bone strength.

Fracture risk in hypothyroid patients is debated, and since the effects of hypothyroidism on bone microarchitecture and strength are unclarified, we investigated these characteristics by high-resolution peripheral quantitative computed tomography (HR-pQCT). Two approaches were used: a cross-sectional control study, comparing 32 hypothyroid women (mean age; 47 ± 12 years) suffering from Hashimoto's thyroiditis with 32 sex-, age-, and menopause-matched healthy controls; a prospective study, where 27 of the women were reexamined 1 year after restoration of euthyroidism. HR-pQCT of the distal radius and tibia, and dual-energy X-ray absorptiometry (DXA) of the spine and hip were performed. Bone strength was estimated using a finite element analysis (FEA). Cross-sectional control study: in the radius, total (mean 14.6 ± 29.3% (SD); p = 0.04) and trabecular bone areas (19.8 ± 37.1%, p = 0.04) were higher, and cortical volumetric bone mineral density (vBMD) lower (-2.2 ± 6.5%, p = 0.032) in hypothyroid patients than in controls. All indices of tibia cortical and trabecular vBMD, microarchitecture, and estimated bone strength were similar between groups, as was hip and spine areal BMD (aBMD). Prospective study: in the radius, mean cortical (-0.9 ± 1.8%, p = 0.02) and trabecular (-1.5 ± 4.6%, p = 0.02) vBMD decreased, and cortical porosity increased (18.9 ± 32.7%, p = 0.02). In the tibia, mean total vBMD (-1.1 ± 1.9%, p = 0.01) and cortical vBMD (-0.8 ± 1.4%, p = 0.01) decreased, while cortical porosity (8.2 ± 11.5%, p = 0.002) and trabecular area (0.2 ± 0.6%, p = 0.047) increased. No changes in FEA were detected. Lumbar spine aBMD decreased (-1.3 ± 3.0%, p = 0.04). Hypothyroidism was associated with an increased trabecular bone area and a lower mineral density of cortical bone in the radius, as assessed by HR-pQCT. Restoration of euthyroidism mainly increased cortical porosity, while estimated bone strength was unaffected.

Bone density, microarchitecture and strength estimates in white versus African American youth with obesity.

African Americans (AA) have more favorable bone density and microarchitecture compared to Whites (W), which may explain their observed lower fracture rates. Obesity has deleterious effects on bone microarchitecture and strength estimates and is associated with an increase in fracture risk. Adolescence and young adulthood are periods of active bone accrual and also periods characterized by an increasing prevalence of obesity. The effect of obesity on the relationship between race and bone parameters remains unclear, particularly in youth. To assess differences in BMD, bone microarchitecture and strength estimates in AA and W adolescents and young adults with moderate to severe obesity. We hypothesized that racial differences in bone endpoints in lean youth would also be noted in youth with moderate to severe obesity. We evaluated 24 AA and 48W adolescent and young adults with a mean age of 18.2±2.4years and a median body mass index (BMI) of 44.8 (40.5-49.4) kg/m2 who underwent dual energy X-ray absorptiometry (DXA), high resolution peripheral quantitative computed tomography (HRpQCT), extended cortical analysis (ECA) and micro-finite element analysis (FEA) to obtain measures of volumetric bone mineral density (vBMD), bone geometry, microarchitecture, and strength estimates at the distal radius and tibia. We found no differences between AA and W for total fat and lean mass, and areal BMD Z-scores (p>0.05 for all). At the distal radius, no significant differences were detected in vBMD, bone geometry or microarchitecture (p>0.05 for all); however, stiffness and failure load were higher in the AA group (p=0.031 and 0.047 respectively). At the distal tibia, cortical vBMD was higher in AA vs. W (p=0.012), while trabecular number was higher and trabecular separation lower in W vs. AA (p≤0.028). Stiffness and failure load trended higher in AA vs. W (p=0.052 and p=0.048, respectively). Groups did not differ for any other bone parameter (p>0.05). Racial differences in bone endpoints appear to be less marked in those with moderate to severe obesity, suggesting that effects of obesity may blunt the effect of race on bone endpoints.

Deterioration of bone microstructure by aging and menopause in Japanese healthy women: analysis by HR-pQCT.

Second-generation high-resolution peripheral quantitative computed tomography (HR-pQCT) has provide higher quality of bone images with a voxel size of 61µm, enabling direct measurements of trabecular thickness. In addition to the standard parameters, the non-metric trabecular parameters such as trabecular morphology (plate to rod-like structures), connectivity, and anisotropy can also be analyzed. The purpose of this study is to investigate deterioration of bone microstructure in healthy Japanese women by measuring standard and non-metric parameters using HR-pQCT. Study participants were 61 healthy Japanese women (31-70years). The distal radius and tibia were scanned using second-generation HR-pQCT, and microstructures of trabecular and cortical bone were measured. Non-metric trabecular parameters included structure model index (SMI), trabecular bone pattern factor (TBPf), connectivity density (Conn.D), number of nodes (N.Nd/TV), degree of anisotropy (DA), and star volume of marrow space (V*ms). Estimated bone strength was evaluated by micro finite element analysis. Associations between bone microstructure, estimated bone strength, age, and menopause were analyzed. Trabecular number declined with age, and trabecular separation increased. SMI and TBPf increased, Conn.D and N.Nd/TV declined, and V*ms increased. Cortical BMD and thickness declined with age, and porosity increased. Stiffness and failure load decreased with age. Cortical thickness and estimated bone strength were affected by menopause. Cortical thickness was most associated with estimated bone strength. Trabecular and cortical bone microstructure were deteriorated markedly with age. Cortical thickness decreased after menopause and was most related to bone strength. Non-metric parameters give additional information about osteoporotic changes of trabecular bone.

Quantitative Ultrasound - An Epidemiological Tool to Uncover the Influence of Lifestyle Factors &amp; its Associated Co Morbidities on Bone Density

Osteoporosis, the metabolic disorder has become a global epidemic1 with increase in life expectancy and changing life style. Quantitative ultrasound is a cheap, non invasive, portable and convenient method to estimate bone strength without any radiation hazard.2–5 The aim of our study is to estimate the bone mineral density by using quantitative ultrasound, look for the influence of parameters like lifestyle factors, comorbidities, chronic drug intake, and other risk factors on BMD; and compare the results with those in the literature done with DEXA scans. In our study of 516 subjects, (i) BMD measures varied from -5.6 to +.5.55 with a mean of -1.8. (ii) BMD decreased significantly with age (r=.351, p<0.0001), (iii) Low BMD was associated with increase in Fragility fractures (p=.007) (iv) Antacid intake, which was pretty common in our subjects (28.7%) led to decrease in BMD (p<.005). (v) Diabetes significantly reduced BMD (p<.005). (vi) Increase in BMI led to significant increase in BMD (r=.166, p<.0001). (vii) BMD increased significantly with increase in physical activity (r=.148, p<.001). Most of the associations found in our study, except that with diabetes, were similar to those consistently associated with BMD as measured with DEXA scans.6–15 Our study suggests the use of Quantitative ultrasound as powerful epidemiological tool with similar outcome measures to DEXA scan without any radiation hazards.

SUN-LB74 Radiofrequency Echographic Multi-Spectrometry (REMS) for the Assessment of Bone Strength and Fracture Risk Prediction

Introduction Fragility bone fractures impact patient’s quality of life and worldwide healthcare systems: accurate technologies and device are required in order to early diagnose and monitor the effect of osteoporosis on a mass-population basis. Several studied have analysed the pros and cons of the numerous technologies available nowadays for the diagnosis and monitoring of bone health, highlighting the need of further tools able to better define and estimate bone strength and to predict the risk of fracture [1]. Objectives The aim is to assess the state of the art about Radiofrequency Echographic Multi-Spectrometry (REMS). Methods A review of the available literature was performed, considering full papers, reviews and abstracts on REMS published before January 31th 2020. Results REMS has been recently presented by an ESCEO consensus paper as a valuable technology for osteoporosis diagnosis and fracture risk estimation [1]. It is based on the automatic processing of the raw unfiltered signals obtained with an ultrasound scan, thus overcoming the main drawback of dual-energy X-ray absorptiometry (DXA) and computed tomography (CT)-based technologies [2]. Moreover, REMS scans are performed at axial skeleton reference sites, i.e. lumbar spine [3] and femoral neck [4], differently from quantitative ultrasound (QUS) technology, which is usually applied to peripheral sites [3]. Clinical performance has been confirmed by a multicentre clinical trial enrolling over 1900 Caucasian women, demonstrating a high correlation between bone mineral density (BMD) estimated by REMS and DXA. In addition, high performance in terms of precision and intra- and inter-operator repeatability of REMS have been assessed [6]. Prospective studies have demonstrated the predictive ability of incident fragility fractures [7] and the high concordance with DXA in terms of measured BMD in patients with rheumatoid arthritis and pre/post-menopause [8, 9]. Conclusions REMS is an innovative approach for the early diagnosis, short-term monitoring of osteoporosis and risk fracture prediction. The available data envisaged for further applications in paediatric patients, pregnant women and patients at risk of secondary osteoporosis (e.g., diabetic, nephropathic, oncological patients). The EchoS system, a device implementing the REMS technology, has recently received the approval from the U.S. Food and Drug Administration (FDA).

OR22-06 Bone Outcomes Following Sleeve Gastrectomy in Adolescents and Young Adults with Obesity Versus Non-Surgical Controls

Background: Sleeve gastrectomy is the most commonly performed weight loss surgery in adolescents with moderate-to-severe obesity. While studies in adults have reported on the deleterious effects of gastric bypass surgery on bone structure and strength estimates, data are lacking for the impact of sleeve gastrectomy on these measures in adolescents. Objective: To evaluate the impact of sleeve gastrectomy on bone outcomes in adolescents and young adults over 12 months using dual energy x-ray absorptiometry (DXA) and high resolution peripheral quantitative computed tomography (HRpQCT). Participants and Methods: We enrolled 33 youth 14-22 years old with moderate to severe obesity; 17 underwent sleeve gastrectomy and 16 were followed without surgery. DXA was used to assess areal bone mineral density (aBMD). HRpQCT was used to assess bone geometry, microarchitecture and volumetric BMD (vBMD) and finite element analysis to assess strength estimates (stiffness and failure load) at the distal tibia and distal radius at baseline and 12 months. 25(OH) vitamin D (25OHD) levels were obtained at baseline and follow-up. Results: The surgical group lost 28.2% of total body weight compared to 1.4% in the non-surgical group. The groups did not differ for changes in 25OHD levels (P=0.181). After controlling for age and sex, compared to the non-surgical group, the surgical group had reductions in aBMD Z-scores at the femoral neck and total hip (p≤ 0.0005). At the distal tibia, there were reductions in cortical thickness and trabecular number, and increases in trabecular separation and cortical vBMD, without changes in strength estimates in the surgical group vs. controls (p≤0.043). Changes were less marked at the distal radius. While sleeve gastrectomy resulted in deleterious effects on most bone parameters, there was an increase in cortical vBMD at both sites, possibly from a decrease in cortical porosity. Most differences were attenuated after adjusting for changes in BMI over 12 months. Conclusions: Over 12 months, weight loss associated with sleeve gastrectomy in adolescents had deleterious effects on areal BMD, bone geometry and trabecular microarchitecture at weight-bearing sites. However, strength estimates did not decrease, possibly because of a simultaneous increase in cortical volumetric BMD. Additional research is necessary to determine the relative contribution(s) of weight loss and the metabolic effects of surgery, and whether the observed effects on bone stabilize or progress over time.

Deficits in Bone Geometry in Growth Hormone-Deficient Prepubertal Boys Revealed by High-Resolution Peripheral Quantitative Computed Tomography

Introduction: Although growth hormone (GH) is essential for attainment of peak bone mass, bone health in prepubertal children with GH deficiency is not routinely evaluated. The objective of this study was to evaluate bone microarchitecture in GH-deficient (GHD) boys using high-resolution peripheral quantitative computed tomography (HR-pQCT). Methods: Fifteen control and fifteen GHD, GH naïve pre-pubertal boys were recruited for a case-control study at a major academic center. Subjects with panhypopituitarism, chromosomal pathology, chronic steroids, or stimulant use were excluded. Volumetric bone mineral density (vBMD; total, cortical, and trabecular), bone geometry (total, cortical and trabecular cross-sectional area, cortical perimeter), bone microarchitecture, and estimated bone strength of the distal radius and tibia were assessed by HR-pQCT. Areal BMD and body composition were assessed by DXA. Insulin-like growth factor 1 (IGF-1), osteocalcin, C telopeptide, and P1NP levels were measured. Results: GHD subjects had a significantly smaller cortical perimeter of the distal radius compared to controls (p < 0.001), with the difference in cortical perimeter persisting after adjusting for height z score, age, lean mass, and 25-hydroxyvitamin D level (p < 0.05).No significant differences were found in vBMD. No significant differences were found in microarchitecture, estimated strength, areal BMD, body composition, or bone turnover markers. Analysis showed significant positive correlations between IGF-1 levels and cortical parameters. Discussion/Conclusions: Prepubertal GHD boys had deficits in bone geometry not evident with DXA. Larger prospective/longitudinal HR-pQCT studies are needed to determine the extent of these deficits, the need for routine bone evaluation, and the timing of GH replacement for prevention or restoration of these deficits.

Potential applications for rhIGF-I: Bone disease and IGF[sbnd

Growth hormone (GH) and insulin like growth factor-I (IGFI) are key bone trophic hormones, whose rising levels during puberty are critical for pubertal bone accrual. Conditions of GH deficiency and genetic resistance impact cortical and trabecular bone deleteriously with reduced estimates of bone strength. In humans, conditions of undernutrition (as in anorexia nervosa (AN), or subsequent to chronic illnesses) are associated with low IGF-I levels, which correlate with disease severity, and also with lower bone mineral density (BMD), impaired bone structure and lower strength estimates. In adolescents and adults with AN, studies have demonstrated a nutritionally acquired GH resistance with low IGF-I levels despite high concentrations of GH. IGF-I levels go up with increasing body weight, and are associated with rising levels of bone turnover markers. In short-term studies lasting 6–10 days, recombinant human IGF-I (rhIGF-I) administration in physiologic replacement doses normalized IGF-I levels and increased levels of bone formation markers in both adults and adolescents with AN. In a randomized controlled trial in adults with AN in which participants were randomized to one of four arms: (i) rhIGF-I with oral estrogen-progesterone (EP), (ii) rhIGF-I alone, (iii) EP alone, or (iv) neither for 9 months, a significant increase in bone formation markers was noted in the groups that received rhIGF-I, and a significant decrease in bone resorption markers in the groups that received EP. The group that received both rhIGF-I and EP had a significant increase in bone density at the spine and hip compared to the group that received neither. Side effects were minimal, with no documented fingerstick glucose of <50 mg/dl. These data thus suggest a potential role for rhIGF-I administration in optimizing bone accrual in states of undernutrition associated with low IGF-I.

Impaired Bone Microarchitecture and Lower Estimated Bone Strength in Children with Type 1 Diabetes

Objective: To evaluate peripheral bone geometry, volumetric bone mineral density (vBMD) and microarchitecture, and to estimate bone strength in children and adolescents with type 1 diabetes. Design and Methods: In a cross-sectional study, high resolution peripheral quantitative CT (HR-pQCT) was performed of the radius and tibia in 84 children with type 1 diabetes and 55 healthy control siblings. Estimated bone strength was assessed using a micro-finite element analysis solver. Multivariate regression analyses were performed adjusting for age, sex, height and body mass index. Results: The median age was 13.2 years in the diabetes group vs. 11.5 years in controls. The median (range) diabetes duration was 4.2 (0.4;15.9) years; median (range) latest year Hb1Ac was 7.8 (5.9;11.8) % (61.8 (41;106) mmol/mol). In adjusted analyses, type 1 diabetes patients had reduced estimated bone strength (failure load) in radius, -324.4 (-545.7;-103.1) kN, p=.004, and tibia, -753.3 (-1149;-357.7) kN, p< .001. In the radius and tibia, children with type 1 diabetes had reduced cortical area, trabecular vBMD, trabecular number and trabecular bone volume fraction and increased trabecular inhomogeneity, adjusted p<.05 for all. Latest year HbA1c was negatively associated with bone microarchitecture (radius and tibia), and with trabecular vBMD and estimated bone strength (tibia). Conclusion: Children with type 1 diabetes had reduced bone sizes, trabecular vBMD and estimated bone strength and adverse microarchitecture, inversely correlated to higher last year HbA1c levels. HR-pQCT holds potential to identify early adverse bone changes and to explain the increased fracture risk in young type 1 diabetes patients. Funding Statement: This study was supported financially by The Consultant’s Research Fund at Odense University Hospital (ID: A1869). Declaration of Interests: The authors have no conflict of interest to declare. Ethics Approval Statement: The study was approved by the Regional Ethical Committee of Southern Denmark (ProjectID: S-20160159) and the Data Protection Agency (Journal nr:18/44863).

Continuous decline in bone mineral density and deterioration of bone microarchitecture 7 years after Roux-en-Y gastric bypass surgery.

ObjectiveRoux-en-Y-gastric bypass (RYGB) surgery is an effective treatment for morbid obesity. A possible overlooked side effect is negative bone metabolic consequences. DesignA seven-year prospective study following ten women and seven men after RYGB (baseline mean age 43 ± 8 years, BMI 42 ± 6 kg/m2).MethodsLumbar spine and total hip bone mineral density (BMD) using dual energy x-ray absorptiometry, distal radius and tibia bone geometry, volumetric BMD, microarchitecture and finite element estimated bone strength using high-resolution peripheral quantitative CT and biochemical markers of bone remodelling were assessed at baseline, 2 and 7 years.ResultsCompared to baseline, body weight was 24 ± 10% lower after 2 years and 21 ± 11% after 7 years. During the 7 years of follow-up, radius and tibia vBMD had declined 13 ± 8% and 8 ± 7% from baseline to 2 years and further 10 ± 7% and 7 ± 8% from 2 to 7 years (all P < 0.001). At both radius and tibia, cortical thickness declined and cortical porosity increased. From baseline to 7 years, there were clear indications of deteriorations of the trabecular network with fewer, more widely spaced and more in-homogeneously distributed trabeculae in both radius and tibia. Overall, declines in estimated bone strength of 16 ± 9% in radius and 16 ± 7% in tibia were observed (both P < 0.001).ConclusionSeven years after RYGB, evidence of continuous declines in BMD and ongoing deterioration of bone microarchitecture and reduced estimated bone strength compared to baseline and 2 years post-surgery results were found. These findings emphasize the need for regular assessment of bone health in patients with prior RYGB.

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

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.

Hip geometry on femoral neck bone strength; a review article

Introduction: Low bone strength of the hip, which depends on both bone mass and bone geometry, leads to risk for fragility hip fracture. Anatomical adaptations of the proximal femoral structure are important to maintain higher bone strength because they predict the fracture risk independent of bone mass. Therefore, it is crucial to evaluate the bone strength of proximal femur to predict the likelihood of fragility fracture risk based on both bone mass and geometric adaptations, as well as the biomechanical strength of femoral neck (FN). Aim: To discuss the literature on geometric indices and biomechanical indices of the proximal femur to estimate FN strength. Material and methods: Dual energy xray absorptiometry (DXA) based hip structural analysis (HSA) technique derived indices of FN geometric adaptations and biomechanical strength at FN and their impact on FN bone strength were explored using the existing literature. Bone mineral content (BMC, gram) and areal bone mineral density (aBMD, g/cm2) can be measured using the HAS technique. The simple hip geometric indices such as hip axis length (HAL), femoral neck length (FNL), neck shaft angle (NSA), FN diameters, FN width and biomechanical indices such as cross-sectional moment of inertia (CSMI, cm4), section modulus (Z, cm3) and cross-sectional area (CSA, cm2) can be estimated using the HSA technique to estimate FN bone strength. Conclusion: Estimation of FN bone strength by HSA based geometric adaptations and biomechanical strength indices provides better understanding of bone strength at FN. HAL and FN bone size with BMD provide better hip fracture predictability.

Factors associated with bone microstructural alterations assessed by HR-pQCT in long-term HIV-infected individuals.

In adults with long-term HIV infection, low bone density and increased fracture risk have emerged as significant comorbidities. Our aim was to assess the association of exercise, nutrition, and medications with bone quality in adults with long-term HIV infection. Forty-three adults with HIV infection were enrolled (median BMI 25.7, range 18.2-35.6kg/m2; median age 57, range 50-69years). Participants underwent ultradistal radius and tibia high-resolution peripheral quantitative CT (HR-pQCT). Questionnaires included the revised Community Healthy Activities Model Program for Seniors (CHAMPS), the Mini Nutritional Assessment (MNA) as well as medication assessments. Multivariable linear regression models were used to evaluate the association of exercise, nutritional status, tenofovir disoproxil fumarate (TDF) and protease inhibitor (PI) use with bone density and microstructure, adjusting for demographic risk factors. In regression models, higher nutrition scores were associated with higher tibia cortical thickness (R2=0.23; β=0.03; p=0.044) and higher radius cortical BMD (R2=0.43; β=8.4; p=0.026). Higher weekly frequency of all physical activities was significantly associated with higher radius trabecular BMD (R2=0.38; β=0.96; p=0.050), higher radius trabecular number (R2=0.31; β=0.01; p=0.026), lower tibia and radius trabecular separation (tibia: R2=0.30; β=-0.003; p=0.038; radius: R2=0.35; β=-0.003; p=0.021), and higher radius bone stiffness (R2=0.45; β=0.38; p=0.047). Higher frequency of bone loading physical activities was significantly associated with higher tibia trabecular density (R2=0.44; β=4.06; p=0.036), higher tibia bone stiffness (R2=0.46; β=3.06; p=0.050), and higher tibia estimated failure load (R2=0.46; β=0.17; p=0.049). TDF used in combination with a PI was associated with lower radius trabecular BMD (R2=0.39; β=-41.2; p=0.042), lower radius trabecular number (R2=0.34; β=-0.44; p=0.009) and greater radius trabecular separation (R2=0.42; β=0.16; p=0.002), while TDF use without a PI was not associated with reduced bone quality. In adults with HIV infection, malnutrition is associated with poor cortical bone quality, while reduced frequency of physical activities and specifically reduced frequency of mechanical loading activities are associated with deficient trabecular bone structure and reduced estimates of bone strength. TDF use in combination with a PI is associated with deleterious effects on trabecular bone structure.