Greater Bone Mineral Density Research Articles

Associations of different dietary patterns, bone mineral density, and fracture risk among elderly women: the China Osteoporosis Prevalence Study.

Despite the fact that China amounts to one-fifth of the world's population, has a higher proportion of the elderly, and has a higher prevalence of osteoporosis and fracture, limited studies have investigated the association between dietary patterns and bone mineral density (BMD) as well as fracture risk among the elderly Chinese population. We aimed to investigate the association between different dietary patterns and BMD as well as the risk of fractures, and this association may vary between elderly women and men. Building upon the China Osteoporosis Prevalence Study, we included 17,489 subjects aged ≥40 years old randomly sampled across 44 counties/districts of 11 provinces or municipalities in China who completed a food frequency questionnaire. BMD was measured by dual x-ray absorptiometry. Vertebral fracture was defined based on lateral spine radiographs using the semi-quantitative technique of Genant. A diet rich in "carnivorous", "vegetarian", "dairy, fruit, and egg" was significantly associated with higher BMD at total hip (TH), femoral neck (FN), and lumbar spine 1-4 (L1-4). Yet, a diet rich in "beverage and fried food" was associated with a lower BMD at the FN and L1-4. High quartiles of the carnivorous diet were associated with 34%-39% reduced risk of clinical fracture in the past 5 years and vertebral fracture. Stronger associations were observed among women. Sensitivity analysis among postmenopausal women presented even stronger positive associations between carnivorous and vegetarian diets and high BMD, as well as between carnivorous diet and reduced risk of fractures. Our study suggested that a diet rich in meat, vegetables, and dairy, fruit, and eggs might be associated with greater BMD and a lower fracture risk, while beverage and fried foods may be associated with a lower BMD at L1-4, especially among elderly women. These findings are relevant to provide recommendations on dietary nutrition regarding the elderly population at high risk of osteoporosis and fractures, especially postmenopausal women.

Prior Nonmelanoma Skin Cancer is Associated with Fewer Fractures, More Vitamin D Sufficiency, Greater Bone Mineral Density, and Improved Bone Microarchitecture in Older Adults

BackgroundPrior nonmelanoma skin cancer (NMSC), a biomarker of cumulative lifetime sun exposure, is associated with reduced fracture risk later in life. The mechanism is unknown. MethodsProspective cohort analysis of 1099 community-dwelling adults aged 50-80 years with baseline and 10-year follow-up assessments. Histopathologically-confirmed NMSC diagnosis was established by linkage with the Tasmanian Cancer Registry. Bone mineral density (BMD) and vertebral deformity were quantified by DXA, 25-hydroxyvitamin D (25(OH)D) by radioimmunoassay, bone microarchitecture by high-resolution peripheral quantitative CT, melanin density by spectrophotometry, and skin photosensitivity and clinical fracture by questionnaire. 25(OH)D <50 nmol/L was considered deficient. ResultsParticipants with an NMSC reported prior to baseline were less likely to sustain an incident vertebral deformity over 10 years (RR = 0.74, P = .036). There were similar reductions for other fracture types but these did not reach significance. Prior NMSC was associated with baseline (RR = 1.23, P = .005) and 10-year longitudinal (RR = 5.9, P = .014) vitamin D sufficiency and greater total body BMD (β = 0.021g/cm2, P = .034), but not falls risk or muscle strength. The relationship between prior NMSC and bone microarchitecture was age-dependent (pinteraction < 0.05). In the oldest age tertile, prior NMSC was associated with greater volumetric BMD (β = 57.8-62.6, P = .002-0.01) and less porosity (β = −4.6 to −5.2, P = .002-0.009) at cortical, compact cortical and outer transitional zones. ConclusionsPrior NMSC was associated with fewer incident fractures in community-dwelling older adults. This protective association is most likely mediated by modifiable fracture risk factors associated with an outdoor lifestyle, including 25(OH)D, BMD, and bone microarchitecture.

Comparison of bone mineral density of runners with inactive males: A cross-sectional 4HAIE study.

The purpose of the study was to determine whether running is associated with greater bone mineral density (BMD) by comparing the BMD of regularly active male runners (AR) with inactive nonrunner male controls (INC). This cross-sectional study recruited 327 male AR and 212 male INC (aged 18-65) via a stratified recruitment strategy. BMD of the whole body (WB) and partial segments (spine, lumbar spine (LS), leg, hip, femoral neck (FN), and arm for each side) were measured by dual-energy x-ray absorptiometry (DXA) and lower leg dominance (dominant-D/nondominant-ND) was established by functional testing. An ANCOVA was used to compare AR and INC. The AR had greater BMD for all segments of the lower limb (p<0.05), but similar BMD for all segments of the upper limb (p>0.05) compared with INC. Based on the pairwise comparison of age groups, AR had greater BMD of the ND leg in every age group compared with INC (p<0.05). AR had grater BMD of the D leg in every age group except for (26-35 and 56-65) compare with INC (p<0.05). In the youngest age group (18-25), AR had greater BMD in every measured part of lower extremities (legs, hips, femoral necks) compared with INC (p<0.05). In the 46-55 age group AR had greater BMD than INC (p < 0.05) only in the WB, D Leg, D neck, and ND leg. In the 56-65 age group AR had greater BMD than INC (p<0.05) only in the ND leg. Overall, AR had greater BMD compared with INC in all examined sites except for the upper limbs, supporting the notion that running may positively affect bone parameters. However, the benefits differ in the skeletal sites specifically, as the legs had the highest BMD difference between AR and INC. Moreover, the increase in BMD from running decreased with age.

Bone mineral density and muscle mass associated with healthy eating index in postmenopausal women; results from RaNCD cohort study

BackgroundThe Healthy Eating Index 2015 (HEI-2015) is a tool for checking the quality of diet. This index is used to examine how well people’s dietary behavior fits certain criteria for achieving a healthy diet in Dietary Guidelines for Americans 2015-2020. We look at the possible association between the HEI-2015 and bone mineral density (BMD) and muscle strength in postmenopausal women.MethodsThis research included 1012 postmenopausal women from the recruitment phase of the Ravansar Noncommunicable Diseases (RaNCD) cohort study in Kermanshah-Iran. A standardized and repeatable food-frequency questionnaire (FFQ) that contains 118 items was used to quantify dietary consumption. Anthropometric indices measured via Bio-Impedance Analyzer BIA (Inbody 770, Inbody Co, Seoul, Korea).ResultThe mean age of postmenopausal women was (56.41 ± 5.31) years. Participants in the highest quartile had a more daily energy intake compared to the lowest quartile (2329.89 ± 837.59), (P < 0.001). Women in the upper quartiles had greater Skeletal Muscle Mass (SMM) than those in the lower quartiles (21.61 ± 2.80 vs 20.52 ± 3.13; p = 0.0002). The linear model didn’t show a significant relationship between HEI score and greater BMD (β = 0.0014, P = 0.169).ConclusionA diet of high quality followed by a high HEL-2015 score was shown to be strongly connected to increased BMD and muscle mass in Kurdish postmenopausal women.

256 Evaluation Calcium and Phosphorus Ratios in the Presence of Phytase on Performance and Whole-Body Bone Mineralization in Growing Pigs

Abstract The objective of this study was to evaluate the effects of dietary calcium and phosphorus ratios in the presence of super dose phytase on grower pigs growth performance and bone mineral density. In two replicates, a total of 48 mixed sex pigs (26.7 kg BW) were allotted by BW and sex into individual pens across 3 dietary treatments (16 pigs/treatment) for 28 days. All diets contain phytase at 1,500 FTU/kg of complete feed and the three diet treatments were formulated with differing levels of Ca to achieve 0.7, 1.1 and 1.5 total Ca:total P. All diets were formulated to be isocaloric and isonitrogenous and ratios were achieved by vary limestone and sand. Pig BW and feed disappearance were recorded at the start (d 0) and end (d 28) of the study to calculate ADG, ADFI and G:F. On day 28, all pigs were euthanized to determine whole body bone, foot, rib, femur and tibia bone mineral density via dual x-ray absorptiometry. Data were analyzed with pen as the experimental unit, fixed effect of dietary treatment, sex and their interaction, and initial BW block and repartition as random effects. Differences were determined significant at P ≤ 0.05. Pig ADG was increased in the 1.1 verses 0.7 and 1.5 Ca:P diets (1.01, 0.95 and 0.95 kg/d, respectively, P = 0.046). End body weight was not different in the 0.7, 1.12 and 1.5 Ca:P treatments (53.5, 54.8 and 53.1 kg, respectively, P = 0.106). Diet Ca:P ratio did not alter ADFI or G:F. Whole body, tibia and femur bone mineral density was increased by 110% in 1.5 verses 0.7 Ca:P fed pigs, with bone mineral density being intermediated in the 1.1 Ca:P diets. Whole body (0.740, 0.752, 0.797, g/cm2, for 0.7, 1.1 and 1.5 Ca:P respectively, P = 0.033). For 0.7, 1.1 and 1.5 Ca:P femurs, bone mineral density was 0.463, 0.498 and 0.516, respectively, P = 0.034). Dietary treatment did not alter whole foot or 10th rib bone mineral densities (P &amp;gt; 0.05). Sex did not affect pig performance, but gilts had a 9% increase in bone mineral content. In conclusion, formulating dietary Ca:P in the presence of super dosing phytase at 1.1:1 total Ca:P resulted in the best ADG, but a ratio of 1.5:1 had the greatest bone mineral density.

526 Dietary fat intake is associated with greater bone mineral density and lean mass in adults with cystic fibrosis

526 Dietary fat intake is associated with greater bone mineral density and lean mass in adults with cystic fibrosis

200 Higher bone mineral density in prediabetes, diabetes and with increasing HbA1c in older Irish adults: results from the TUDA study

Abstract Background Patients with type II diabetes have higher Bone Mineral Density (BMD) but paradoxically have an increased fracture risk. However, less is known about the relationship between prediabetes and BMD or fracture risk. We aimed to evaluate the relationship between pre-diabetes, diabetes, HbA1c and BMD in older Irish adults. Methods Study participants were from a large cross-sectional study of adults aged &amp;gt;60 years; Trinity Ulster University Department of Agriculture (TUDA) study. Patients on treatment for osteoporosis, current or previous long-term glucocorticoids, aromatase inhibitors or androgen deprivation therapy were excluded. Diabetes was defined by self-report, use of diabetic medications or HBA1c ≥6.5% and after excluding same, prediabetes was defined as a HbA1c of 5.7–6.4%[1]. BMD was measured by DXA at the total hip and lumbar spine. The relationship between prediabetes, diabetes, HbA1c and BMD was explored in regression models. Results There were 2,127 participants and mean age was 70.0 ± 6.5 with 57.9% female. 17.7% had diabetes and 26% prediabetes. Compared to normoglycaemic participants, diabetics had higher BMD at the hip (p &amp;lt; 0.001) and spine (p = 0.007) and prediabetics higher BMD at the hip (p &amp;lt; 0.001) after adjusting for age, sex, body mass index, serum vitamin D, eGFR, smoking, alcohol intake and timed up and go. In multivariate analysis, increasing HbA1c in non-diabetics was also associated with greater BMD at the hip (p = 0.001) but not the spine. Conclusion This study demonstrates that BMD is increased in older adults with both diabetes and prediabetes and with increasing HbA1c in non-diabetics. Despite this, BMD is known to underestimate fracture risk in diabetics where a lower treatment threshold for starting osteoporosis medications is recommended. This might also hold true in prediabetes where altered BMD could affect material bone quality and fracture risk though studies are conflicting and more research is required.

A biomechanical study to optimize superior capsular reconstruction operative technique

The goals of this study were to optimize superior capsular reconstruction by assessing the relative fixation strength of 4 suture anchors; evaluating 3 glenoid neck locations for fixation strength and bone mineral density (BMD); determining if there is a correlation between BMD and fixation strength; and determining which portal sites have optimal access to the posterosuperior and anterosuperior glenoid neck for anchor placement. Twenty cadaveric specimens were randomized into 4 groups: all-suture anchor (FiberTak), conventional 3.0-mm knotless suture anchor (SutureTak), 3.9-mm knotless PEEK (polyetheretherketone) Corkscrew anchor, and 4.5-mm Bio-Corkscrew anchor. Each specimen was prepared with 3 anchors into the glenoid: an anterosuperior anchor, superior anchor, and posterosuperior anchor. All anchors were inserted into the superior glenoid neck 5 mm from the glenoid rim. A materials testing system performed cyclic testing (250 cycles) followed by load-to-failure testing at 12.5 mm/s. Cyclic elongation, first cycle excursion, maximum load, and stiffness were recorded. Using custom software, BMD was calculated at each anchor location. This software was also used to assess access to the posterosuperior and anterosuperior glenoid neck from standard arthroscopic portal positions. There was no significant difference in cyclic elongation (P=.546), first cycle excursion (P=.476), maximum load (P=.817), or stiffness (P=.309) among glenoid anchor positions. Cyclic elongation was significantly longer in the PEEK Corkscrew group relative to the other implants (P≤.002). First cycle excursion was significantly greater in the FiberTak group relative to all other implants (P≤.008). For load-to-failure testing, the Bio-Corkscrew group achieved the highest maximum load (P≤.001). No other differences in cyclic or failure testing were observed between the groups. No differences in stiffness testing were observed (P=.133). The superior glenoid rim had the greatest BMD (P=.003), but there was no correlation between BMD and cyclic/load outcomes. The posterior portal (80% of specimens) and the anterior portal (60% of specimens) demonstrated the best access to the posterosuperior and anterosuperior glenoid neck, respectively. The 4.5-mm Bio-Corkscrew anchor provided the most robust fixation to the glenoid during superior capsular reconstruction as it demonstrated the strongest maximum load, had minimal elongation, had minimal first cycle excursion, and did not fail during cyclic testing. The superior glenoid neck had the highest BMD; however, there was no correlation between BMD or glenoid anchor location and biomechanical outcomes. The posterior portal and anterior portal provided optimal access to the posterosuperior glenoid neck and anterosuperior glenoid neck, respectively.

Association of Body Composition with Static Plantar Foot Pressure in Young Adult

Body composition is a key component of health-related fitness. Dual Energy Absorptiometry (DEXA) is the most reliable technique to evaluate body composition. There is evidence suggesting that obesity is linked to foot disorders leading to &amp; an increase in the risk of falls and injuries. Pedobarography is a fast, simple, non-invasive and reliable method used to measure plantar foot pressure. Studies on the association of body composition using DEXA with the static standing plantar pressure are limited. Purpose: The purpose of the study was to measure the association of fat percentage, Body mass index, type of obesity, fat mass and bone mineral content (BMC) with foot pressure. Methods: 64 young adults participated in this study including 34 females and 30 males with a mean age of 21.7±2.6 years. DEXA and Pedobarography were used for evaluation. Results: It was found that with the increase in every 1% in fat percentage, BMI, android type obesity the forefoot pressure increases by 1.070% (p-value 0.06), 1.079% (p-value 0.07) and 1.106% (p-value 0.25). Gynoid type obesity has an inverse relationship with forefoot pressure. With every 1% decrease in the gynoid type obesity value the forefoot pressure increases by 0.971% (p-value 0.97). Also, 39 out of 64 (60%) subjects with higher fat mass and 34 out of 64 (53%) subjects with greater bone mineral density (BMD) on one side had foot pressure dominance on the same side with p-value &gt;0.05. Conclusion: This study concludes that body composition parameters variably affect the foot pressure in static standing.

Diabetes Mellitus is Associated with Poor Bone Microarchitecture in Older Adults Residing in Long-Term Care Facilities.

Both diabetes mellitus (DM) and osteoporosis are very common in older adults who reside in long-term care (LTC) facilities. Nevertheless, few studies have examined the relationship between diabetes and bone quality in this population. The purpose of this study is to determine if bone mineral density (BMD) or trabecular bone score (TBS) is a better measure of bone quality and skeletal health, in LTC residents with and without a history of DM. Methodology. In this longitudinal cohort study, we examined baseline BMD (lumbar spine, total hip, and femoral neck), TBS, DM, and functional status in 511 LTC residents who were enrolled in two ongoing randomized placebo-controlled osteoporosis clinical trials. On average, participants were older than 80 years and majority were prefrail or frail. Women with DM had greater lumbar spine BMD (1.106 vs 1.017, adjusted difference ± standard error = 0.084 ± 0.023 g/cm2, p = 0.0003) and femoral neck BMD (0.695 vs 0.651, 0.027 ± 0.013 g/cm2, p = 0.0463), but lesser lumbar spine TBS (1.211 vs 1.266, -0.036 ± 0.016, p = 0.0299) compared to women without DM. Total hip BMD was also higher based on descriptive statistics (0.780 vs 0.734, p = 0.6255) in diabetic women, although the difference was not statistically significant. Men had similar but attenuated findings. Among LTC residents, those with DM have greater BMD but lower bone quality measured by TBS. TBS should be considered in assessing older patients with DM. However, further studies are required to confirm the findings with respect to fractures.

126 CENTRAL ADIPOSITY IS ASSOCIATED WITH INCREASED PREVALENCE OF VERTEBRAL FRACTURES

Abstract Background Increased body weight and obesity are associated with greater bone mineral density (BMD) though effects on fracture risk appear to be site specific. In particular, the relationship between Body Mass Index (BMI), abdominal weight and Vertebral Fractures (VF) is complex. Some studies have found greater incidence of VF's with obesity though results are inconsistent. Recent evidence supports a stronger association between measures of abdominal fat and VF's. We aimed to examine the association between central adiposity and VF's in older Irish adults. Methods Participants were from a large cross-sectional study of older Irish adults (aged &amp;gt;60) attending GP or hospital outpatient services. VF diagnosis was based on self-report (ie. clinical vertebral fracture) so we excluded those with a Mini Mental State Examination (MMSE) &amp;lt; 25. BMD was measured with DXA and patients taking antiresorptive or anabolic therapies were excluded. The relationship of waist hip ratio (a surrogate marker of central adiposity) with VF's was explored in regression models. Results 2055 identified, mean age 69.8 ± 6.3 years (range 60-99), 58.6% female. Vertebral fracture prevalence was 6.3% (n=130). Waist hip ratio was positively associated with presence of a vertebral fracture after adjusting for age, sex, BMI, timed up and go, smoking, serum vitamin D, lumbar spine BMD and steroid use &amp;gt; 3 months (beta: 0.04, P&amp;lt;0.001). Conclusion We identified that central adiposity (as measured by waist/hip ratio) was associated with VF presence independent of several factors including BMI and spine BMD. This suggests that body fat distribution and/or altered bone quality may play a role. Visceral body fat (which is correlated with waist hip ratio) is associated with increased production of adipocytokines, altered vertebral geometry and micro-architecture, increased vertebral bone marrow fat and greater loading forces on the spine, all of which may mediate increased VF risk.

Low dose aspirin associated with greater bone mineral density in older adults

The use of low-dose aspirin in older adults is increasing as is the prevalence of osteoporosis. Aspirin has been shown in numerous studies to affect bone metabolism. However, there is no clear link between low-dose aspirin use and bone mineral density (BMD). This study examined differences in bone mineral density between low-dose aspirin users and non-aspirin users in adults aged 50–80 years. We conducted a cross-sectional study of 15,560 participants who participated in the National Health and Nutrition Examination Survey (NHANES) 2017-March 2020. We used a multivariate logistic regression model to evaluate the relationship between low-dose aspirin and femoral neck BMD, femoral total BMD, intertrochanteric BMD, and the first lumbar vertebra BMD (L1 BMD) in patients aged 50 to 80 years. A total of 1208 (Group 1: femoral neck BMD, total femur BMD, and intertrochanter BMD) and 1228 (Group 2: L1 BMD) adults were included in this study. In both group 1 and group 2, BMD was higher in the low-dose aspirin group than in the non-aspirin group (Total femur BMD β = 0.019, 95% CI 0.004–0.034; Femoral neck BMD β = 0.017, 95% CI 0.002–0.032; Intertrochanter BMD β = 0.025, 95% CI 0.007–0.043; L1 BMD β = 0.026, 95% CI 0.006–0.046). In subgroup analyses stratified by gender, this positive association existed in both gender after adjusting for confounders. On subgroup analyses stratified by age, this positive association existed in three different age groups after adjusting for confounders. To test whether the effect of low-dose aspirin on BMD was affected by gender and age, the interaction P value was greater than 0.05. These findings from a human study looking into the relationship between low-dose aspirin use and BMD suggest that regular low-dose aspirin may be associated with a higher BMD. The association between low-dose aspirin and BMD did not differ by age group or gender.

Efficacy of the Combination of Teriparatide and Denosumab in the Treatment of Postmenopausal Osteoporosis: A Meta-Analysis

Aim: Evidence on the efficacy of combination treatment of teriparatide and denosumab for osteoporosis remains controversial. We aim to compare the efficacy between the combination treatment and monotherapy among patients with postmenopausal osteoporosis. Methods and results: We systematically searched PubMed, EMBASE, the Cochrane Library, and Web of Science up to 26 January 2022, for relevant studies. This meta-analysis reviewed all randomized controlled trials (RCTs) that reported on the combination treatment of teriparatide and denosumab in patients with postmenopausal osteoporosis. The articles were examined individually by two reviewers, and the relevant data was extracted. We combined weighted mean difference (WMD) for bone mineral density (BMD) using random- or fixed- effect models and conducted subgroup analyses. Sensitivity analyses were performed, and possible publication bias was also assessed. Overall, combination treatment enhanced the mean percent change of bone mineral density in lumbar spine than monotherapy (WMD = 2.91, 95%CI: 1.983.83; p = 0.00). And, combination treatment has been beneficial for enhancing the mean percent change of BMD in hip (WMD = 3.19, 95%CI: 2.25∼4.13; p = 0.00). There was no significant difference between combination treatment and monotherapy in terms of the adverse events (RR = 0.81, 95%CI: 0.45∼1.45; p = 0.472). Conclusion: The meta-analysis indicates that combination treatment led to greater BMD at the lumbar spine and hip in comparison to monotherapy, without an increased incidence of adverse events. Systematic Review Registration: (https://inplasy.com/), identifier (Inplasy Protocol 2734).

Clinical study evaluating β-blockers use and fracture risk in patients with primary osteoporosis Running title

Background and objectives: In osteoporosis, low bone mass and growing fragility are main symptoms. BB users had greater BMD and/or decreased fracture risk, according to observational studies. Other studies found no effect of BB on fracture risk and osteoporosis disease. In this study, the effect of selective and non-selective BB on fracture risk in osteoporotic individuals was studied. Methods: A total of fifty osteoporotic patients of both genders were included in this randomized controlled, parallel, and prospective trial. Osteoporotic subjects were divided into three groups: a control group (CG), a non-selective beta-blocker group (NSBB), and a cardio-selective beta-blocker group (CSBB). T-score, fracture risk (FR), bone mineral density (BMD), and bone turnover markers were studied as a result of this investigation. Results: After six months of follow-up, it was discovered that the T-score mean values of the three groups varied significantly. BMD was significantly higher in the group receiving non-selective beta-blockers (NSBB) than in the control group (CG). In the three categories of fracture risk region, the fracture risk was statistically decreased in both the NSBB and CSBB groups. Additionally, both the NSBB and CSBB groups demonstrated a decrease in bone turnover markers (BTM), as contrasted to the control group.

Body composition in individuals with cystic fibrosis

Because nutritional status is intimately linked with pulmonary function and survival, nutrition has been at the mainstay of cystic fibrosis (CF) care. Body Mass Index (BMI) is traditionally used to define nutritional status because of the ease with which it can be calculated, but it has a number of limitations including its inability to differentiate fat mass (FM) from lean body mass (LBM), the latter thought to confer health advantage. A number of tools are available to quantify body composition including dual-energy x-ray absorptiometry (DXA), bioelectrical impedance, MRI, CT, air displacement plethysmography, and stable isotopes, and these have been used to varying degrees in studies of CF. In CF, LBM tends to be lower for a given BMI, particularly at lower BMI. In adults, lower fat-free mass (FFM) correlates with greater CF disease severity, lower pulmonary function and higher inflammatory markers. FFM is also positively associated with greater bone mineral density, while greater FM is associated with greater loss of lumbar spine bone mineral density over 2 years. In youth, LBM is positively associated with pulmonary function. The predictive value of body composition for functional and clinical outcomes and the role of improving LBM on these outcomes remain undefined. With improvements in BMI accompanying highly-effective modulator therapy, closer evaluations of body composition may inform risk for more traditional, non-CF adult outcomes in CF.

The effect of genetically modified platelet-derived growth factor-BB over-expressing mesenchymal stromal cells during core decompression for steroid-associated osteonecrosis of the femoral head in rabbits

BackgroundApproximately one third of patients undergoing core decompression (CD) for early-stage osteonecrosis of the femoral head (ONFH) experience progression of the disease, and subsequently require total hip arthroplasty (THA). Thus, identifying adjunctive treatments to optimize bone regeneration during CD is an unmet clinical need. Platelet-derived growth factor (PDGF)-BB plays a central role in cell growth and differentiation. The aim of this study was to characterize mesenchymal stromal cells (MSCs) that were genetically modified to overexpress PDGF-BB (PDGF-BB-MSCs) in vitro and evaluate their therapeutic effect when injected into the bone tunnel at the time of CD in an in vivo rabbit model of steroid-associated ONFH.MethodsIn vitro studies: Rabbit MSCs were transduced with a lentivirus vector carrying the human PDGF-BB gene under the control of either the cytomegalovirus (CMV) or phosphoglycerate (PGK) promoter. The proliferative rate, PDGF-BB expression level, and osteogenic differentiation capacity of unmodified MSCs, CMV-PDGF-BB-MSCs, and PGK-PDGF-BB-MSCs were assessed. In vivo studies: Twenty-four male New Zealand white rabbits received an intramuscular (IM) injection of methylprednisolone 20 mg/kg. Four weeks later, the rabbits were divided into four groups: the CD group, the hydrogel [HG, (a collagen-alginate mixture)] group, the MSC group, and the PGK-PDGF-BB-MSC group. Eight weeks later, the rabbits were sacrificed, their femurs were harvested, and microCT, mechanical testing, and histological analyses were performed.ResultsIn vitro studies: PGK-PDGF-BB-MSCs proliferated more rapidly than unmodified MSCs (P < 0.001) and CMV-PDGF-BB-MSCs (P < 0.05) at days 3 and 7. CMV-PDGF-BB-MSCs demonstrated greater PDGF-BB expression than PGK-PDGF-BB-MSCs (P < 0.01). However, PGK-PDGF-BB-MSCs exhibited greater alkaline phosphatase staining at 14 days (P < 0.01), and osteogenic differentiation at 28 days (P = 0.07) than CMV-PDGF-BB-MSCs. In vivo: The PGK-PDGF-BB-MSC group had a trend towards greater bone mineral density (BMD) than the CD group (P = 0.074). The PGK-PDGF-BB-MSC group demonstrated significantly lower numbers of empty lacunae (P < 0.001), greater osteoclast density (P < 0.01), and greater angiogenesis (P < 0.01) than the other treatment groups.ConclusionThe use of PGK-PDGF-BB-MSCs as an adjunctive treatment with CD may reduce progression of osteonecrosis and enhance bone regeneration and angiogenesis in the treatment of early-stage ONFH.

Zoledronic acid and bone health in older adults with cognitive impairment.

Osteoporosis has detrimental consequences for frail older adults. The effects on those with both osteoporosis and cognitive impairment are compounded due to increased risk of falls and changes in mobility, both of which can lead to fracture. However, there are limited data on treatment benefits for osteoporotic individuals with cognitive impairment. This post hoc, secondary analysis of data from a randomized, double-blind, placebo-controlled clinical trial of single-dose zoledronic acid included 179 women age ≥ 65 years residing in assisted living facilities or nursing homes, 43 of whom had mild to severe cognitive impairment. We assessed bone mineral density (BMD) of the total hip, femoral neck, and lumbar spine by dual-energy x-ray absorptiometry and serum bone turnover markers (C-terminal telopeptide of type I collagen and procollagen type I N propeptide) at 6 and 12 months. In participants with cognitive impairment, those who received zoledronic acid had 4.3% greater BMD at the total hip (p=.005) and 5.3% greater BMD at the femoral neck (p<.001) after 12 months compared to those in the placebo group. Bone turnover markers demonstrated significant decreases at 6 months in those with cognitive impairment who received active treatment compared to the placebo group. Improvements in bone health measures with zoledronic acid were similar to those seen in participants without cognitive impairment. Zoledronic acid improves bone health in frail older women with cognitive impairment similar to those without impairment. Further studies are warranted to assess the benefit for fracture reduction in this undertreated population.

Type 2 Diabetes and Change in Total Hip Bone Area and Bone Mineral Density in Swedish Men and Women Older Than 55 Years.

ContextIn a cross-sectional study, we found an association between type 2 diabetes mellitus (T2DM) and smaller bone area together with greater bone mineral density (BMD) at the total hip.ObjectiveThis work aims to investigate these associations longitudinally, by studying T2DM status (no T2DM n = 1521, incident T2DM n = 119, or prevalent T2DM n = 106) in relation to changes in total hip bone area and BMD.MethodsIn 3 cohorts, the Swedish Mammography Cohort Clinical (SMCC; n = 1060), Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; n = 483), and Uppsala Longitudinal Study of Adult Men (ULSAM; n = 203), with repeat assessment of T2DM status and dual energy x-ray absorptiometry (DXA) measurements of total hip bone area and BMD on average 8 years apart, a linear regression model was used to assess the effect of T2DM status on change in bone area and BMD at the total hip.ResultsAfter meta-analysis, the change in bone area at the total hip was 0.5% lower among those with incident T2DM compared to those without T2DM (–0.18 cm2; 95% CI, –0.30 to –0.06). The change in bone area was similar among those with prevalent T2DM compared to those without (0.00 cm2; 95% CI, –0.13 to 0.13). For BMD, the combined estimate was 0.004 g/cm2 (95% CI, –0.006 to 0.014) among those with incident T2DM and 0.010 g/cm2 (95% CI, –0.000 to 0.020) among those with prevalent T2DM, compared to those without T2DM.ConclusionThose with incident T2DM have a lower expansion in bone area at the total hip compared to those without T2DM.

Fasting glucose, bone area and bone mineral density: a Mendelian randomisation study

Aims/hypothesisObservational studies indicate that type 2 diabetes mellitus and fasting glucose levels are associated with a greater risk for hip fracture, smaller bone area and higher bone mineral density (BMD). However, these findings may be biased by residual confounding and reverse causation. Mendelian randomisation (MR) utilises genetic variants as instruments for exposures in an attempt to address these biases. Thus, we implemented MR to determine whether fasting glucose levels in individuals without diabetes are causally associated with bone area and BMD at the total hip.MethodsWe selected 35 SNPs strongly associated with fasting glucose (p < 5 × 10−8) in a non-diabetic European-descent population from the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) (n = 133,010). MR was used to assess the associations of genetically predicted fasting glucose concentrations with total hip bone area and BMD in 4966 men and women without diabetes from the Swedish Mammography Cohort, Prospective Investigation of Vasculature in Uppsala Seniors and Uppsala Longitudinal Study of Adult Men.ResultsIn a meta-analysis of the three cohorts, a genetically predicted 1 mmol/l increment of fasting glucose was associated with a 2% smaller total hip bone area (−0.67 cm2 [95% CI −1.30, −0.03; p = 0.039]), yet was also associated, albeit without reaching statistical significance, with a 4% higher total hip BMD (0.040 g/cm2 [95% CI −0.00, 0.07; p = 0.060]).Conclusions/interpretationFasting glucose may be a causal risk factor for smaller bone area at the hip, yet possibly for greater BMD. Further MR studies with larger sample sizes are required to corroborate these findings.Graphical abstract

Correlation between weight-bearing asymmetry and bone mineral density in patients with bilateral knee osteoarthritis

BackgroundAlthough unloading of the joint is related to reduction of the local bone mineral density (BMD), little attention had been paid to the relationship between loading asymmetry and side-to-side difference of BMD in patients with bilateral knee osteoarthritis (OA). The aim of the present study was to evaluate and clarify the relationship between gait parameters and bone mineral density in those patients.MethodsA total of 36 knees in eighteen patients (mean age = 73.7 ± 6.3 years, mean body mass index = 26.7 ± 3.8 kg/m2) with bilateral medial knee OA were enrolled in the present study. All subjects performed relaxed standing and level walking at our gait laboratory after informed consent was obtained. First, ground reaction force was calculated on bilateral knees during standing. The knees in each patient were divided into higher and lower force side for the definition of dominant side limb. Second, gait parameters in each subject were obtained. To analyze the factors that affect the weight-bearing distribution in both limbs, clinical data and biomechanical parameters were compared between knees. Clinical data included radiographic OA grade, femorotibial angle, and BMD at the bilateral femoral neck.ResultsKnees on higher force side were significantly more extended than on lower force side in standing (P = 0.012) and knee excursion during weight acceptance phase in gait was significantly larger in higher side than in lower side (P = 0.006), while the other parameters were not significantly different. As to the clinical data, higher force side had greater BMD, compared to lower force side. In terms of Kellgren–Lawrence scale and femorotibial angle on plain radiographs, there were no significant differences between higher and lower force side.ConclusionsBased on loading asymmetry in the present study, lower BMD was observed on Lower force side in patients with knee OA. Therefore, it is helpful for orthopedic surgeons to examine side-to-side differences of bone mineral density or extension limitation during standing for evaluation of the loading condition in patients with bilateral knee OA.