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Osteoporosis, a disease characterized by progressive bone loss and increased risk of fracture, often results from menopausal loss of estrogen in women. Neuropeptide Y has been shown to negatively regulate bone formation, with amygdala specific deletion of the Y2 receptor resulting in increased bone mass in mice. In this study, ovariectomized (OVX) mice were injected once daily with JNJ-31020028, a brain penetrant Y2 receptor small molecule antagonist to determine the effects on bone formation. Antagonist treated mice had reduced weight and showed increased whole-body bone mineral density compared to vehicle-injected mice. Micro computerized tomography (micro-CT) demonstrated increased vertebral trabecular bone volume, connectivity density and trabecular thickness. Femoral micro-CT analysis revealed increased bone volume within trabecular regions and greater trabecular number, without significant difference in other parameters or within cortical regions. A decrease was seen in serum P1NP, a measure used to confirm positive treatment outcomes in bisphosphonate treated patients. C-terminal telopeptide 1 (CTX-1), a blood biomarker of bone resorption, was decreased in treated animals. The higher bone mineral density observed following Y2 antagonist treatment, as determined by whole-body DEXA scanning, is indicative of either enhanced mineralization or reduced bone loss. Additionally, our findings that ex vivo treatment of bone marrow cells with the Y2 antagonist did not affect osteoblast and osteoclast formation suggests the inhibitor is not affecting these cells directly, and suggests a central role for compound action in this system. Our results support the involvement of Y2R signalling in bone metabolism and give credence to the hypothesis that selective pharmacological manipulation of Y2R may provide anabolic benefits for treating osteoporosis., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Unlabelled: The study aimed to quantify the long-term effects of stroke on tibial bone morphology and hip bone density. Only the trabecular bone mineral density and bone strength index in the hemiparetic tibial distal epiphysis showed a significant decline among individuals who had sustained a stroke 12-24 months ago., Introduction: This study aims to determine the changes in bone density and morphology in lower limb long bones during a 1-year follow-up period and their relationship to muscle function in chronic stroke patients., Methods: Twenty-eight chronic stroke patients (12-166 months after the acute stroke event at initial assessment) and 27 controls underwent bilateral scanning of the hip and tibia using dual-energy X-ray absorptiometry and peripheral quantitative computed tomography, respectively. Each subject was re-assessed 1 year after the initial assessment., Results: Twenty stroke cases and 23 controls completed all assessments. At the end of the follow-up, the paretic tibial distal epiphysis suffered significant decline in trabecular bone density (-1.8 ± 0.6 %, p = 0.006) and bone strength index (-2.7 ± 0.6 %, p < 0.001). More severe decline in the former was associated with poorer leg muscle strength (ρ = 0.447, p = 0.048) and motor recovery (ρ = 0.489, p = 0.029) measured at initial assessment. The loss in trabecular bone density remained significant among those whose stroke onset was 12-24 months ago (p < 0.001), but not among those whose stroke onset was beyond 24 months ago (p > 0.05) at the time of initial assessment. The changes of outcomes in the tibial diaphysis, except for cortical bone mineral content on the non-paretic side (-1.3 ± 0.3 %, p = 0.003), and hip bone density were well within the margin of error for precision., Conclusions: There is evidence of continuous trabecular bone loss in the paretic tibial distal epiphysis among chronic stroke patients, but it tends to plateau after 2 years of stroke onset. The steady state may have been reached earlier in the hip and tibial diaphysis.

Objectives: To describe the changes in bone density and geometry of the radius after chronic stroke and the associated clinical factors., Methods: Twenty stroke patients (12 men and 8 women, age=42-78 years, time post-stroke=12-166 months) and 23 control participants (14 men and 9 women, age=53-77 years) were assessed at the time of enrolment and one year later. Peripheral quantitative computed tomography was used to scan the radius epiphysis (4% site) and diaphysis (33% site). Grip strength, spasticity, paretic arm disuse, physical activity, and vascular health were also evaluated., Results: During the follow-up period, only the cortical thickness and cortical bone mineral content (BMC) in the paretic radius diaphysis showed a decline that exceeded the least significant change value (p=0.002). Paretic arm disuse, lower vascular elasticity and physical activity level at initial assessment were significantly related to more decline in cortical thickness at this site (p<0.01)., Conclusions: The paretic radius diaphysis sustained significant reduction in cortical thickness and cortical BMC over time in chronic stroke, but these changes were less pronounced than those previously reported in sub-acute stroke. Strategies to modify vascular health, disuse, and physical activity may be important in improving upper limb bone health but will need further investigations.

Unlabelled: Chronic stroke survivors with low hip bone density are particularly prone to fractures. This study shows that fear of falling is independently associated with falls in this population. Thus, fear of falling should not be overlooked in the prevention of fragility fractures in these patients., Introduction: Chronic stroke survivors with low bone mineral density (BMD) are particularly prone to fragility fractures. The purpose of this study was to identify the determinants of balance, mobility and falls in this sub-group of stroke patients., Methods: Thirty-nine chronic stroke survivors with low hip BMD (T-score <-1.0) were studied. Each subject was evaluated for the following: balance, mobility, leg muscle strength, spasticity, and fall-related self-efficacy. Any falls in the past 12 months were also recorded. Multiple regression analysis was used to identify the determinants of balance and mobility performance, whereas logistic regression was used to identify the determinants of falls., Results: Multiple regression analysis revealed that after adjusting for basic demographics, fall-related self-efficacy remained independently associated with balance/mobility performance (R2 = 0.494, P < 0.001). Logistic regression showed that fall-related self-efficacy, but not balance and mobility performance, was a significant determinant of falls (odds ratio: 0.18, P = 0.04)., Conclusions: Fall-related self-efficacy, but not mobility and balance performance, was the most important determinant of accidental falls. This psychological factor should not be overlooked in the prevention of fragility fractures among chronic stroke survivors with low hip BMD.

Unlabelled: Bone health status of the radius in individuals with chronic stroke was evaluated using peripheral quantitative computed tomography. Bone mineral density and cortical thickness on the affected side were compromised when compared with the unaffected side. Muscle weakness, spasticity, and disuse were identified as contributing factors to such changes., Introduction: Following a stroke, demineralization and geometric changes occur in bone as a result of disuse and residual impairments, and these can contribute to an increased risk of fragility fractures., Methods: This study used peripheral quantitative computed tomography (pQCT) to evaluate volumetric bone mineral density and geometry at the midshaft radius in people living with chronic stroke. Older individuals with chronic stroke were recruited. Each subject underwent a pQCT scan of the midshaft radius at the 30% site on both upper limbs. Muscle strength, motor function, spasticity, and chronic disuse were also evaluated. Data from 47 subjects (19 women) were assessed., Results: A significant difference was found between the two limbs for cortical bone mineral content, cortical bone mineral density, cortical thickness, and polar stress-strain index. There was no significant side-to-side difference in total bone area. Percent side-to-side difference in muscle strength, spasticity, and chronic disuse were significant determinants of percent side-to-side difference in cortical bone mineral content and cortical thickness., Conclusions: The findings suggest that following chronic stroke, endosteal resorption of the midshaft radius occurred with a preservation of total bone area. Muscle weakness, spasticity, chronic disuse significantly contributed to demineralization and geometric changes in the radius following chronic stroke.

To systematically review available evidence related to the characteristics of bone changes post-stroke and the relationship between various aspects of muscle function (e.g., strength, spasticity) and bone properties after stroke onset. An extensive online database search was undertaken (last search in January 2019). Articles that examined the bone properties in stroke patients were included. The quality of the studies was evaluated with the National Institutes of Health (NIH) Study Quality Assessment Tools. Publication bias of meta-analyses was assessed using the Egger's regression asymmetry test. The selection and evaluation of the articles were conducted by two independent researchers. Fifty-nine studies were identified. In subacute and chronic stroke studies, the skeletal sites in the paretic limbs sustained a more pronounced decline in bone quality than did their counterparts in the non-paretic limbs. The rate of changes showed a decelerating trend as post-stroke duration increased, but the timing of achieving the steady rate differed across skeletal sites. The magnitude of bone changes in the paretic upper limb was more pronounced than the paretic lower limb. There was a strong relationship between muscle strength/mass and bone density/strength index. Muscle spasticity seemed to have a negative impact on bone integrity in the paretic upper limb, but its influence on bone properties in the paretic lower limb was uncertain. Substantial bone changes in the paretic limbs occurred particularly in the first few months after stroke onset. Early intervention, muscle strength training, and long-term management strategies may be important to enhance bone health post-stroke. This review has also revealed the knowledge gaps which should be addressed in future research. [ABSTRACT FROM AUTHOR]

Summary: The influence of various stroke impairments on bone health is poorly understood. This study showed that muscle function and small artery compliance were more strongly associated with the bone strength index at the tibial diaphyseal and epiphyseal regions, respectively. These impairments should be targeted in promoting bone health post-stroke. Introduction: This study examined the bone structural properties of the tibial distal epiphysis and diaphysis after chronic stroke and identified the clinical correlates of the bone strength index measured at these sites. Methods: The tibial distal epiphysis (4 % site) and diaphysis (66 % site) were scanned on both sides in 66 chronic stroke patients and 23 control participants using peripheral quantitative computed tomography. Dynamic knee muscle strength, balance function, spasticity, arterial compliance, and endurance were also measured in the stroke group. Results: At the 4 % site, multivariate analysis showed a significant side × group interaction effect (Wilk's lambda = 3.977, p < 0.001), with significant side-to-side differences in total volumetric bone mineral density (vBMD), trabecular vBMD, and bone strength index in the stroke group, but not in the control group. A significant side × group interaction was also found at the 66 % site (Wilk's lambda = 4.464, p < 0.001), with significant side-to-side differences in cortical vBMD, cortical area, cortical thickness, and bone strength index in the stroke group only. Balance and endurance were independently associated with bone strength index at both tibial sites in the paretic leg ( p < 0.05) after adjusting for relevant factors in multivariate regression analysis. Small artery compliance and muscle strength were significantly associated with the bone strength index at the 4 % site and 66 % site, respectively. Conclusions: The influence of various stroke impairments on bone was region-specific. While muscle function was more strongly associated with the bone strength index in the diaphyseal region, the effect of vascular health was more apparent in the tibial epiphysis in the paretic leg. [ABSTRACT FROM AUTHOR]

Summary: The objective of this study was to examine the associations of neuromuscular and cardiovascular impairments with the bone strength index of the hemiparetic distal radius epiphysis in chronic stroke survivors. The results showed that grip strength is the most predominant predictor of the bone strength index. Introduction: The pupose of the study was to examine the associations of neuromuscular and cardiovascular impairments with the bone strength index of the hemiparetic distal radius epiphysis in chronic stroke survivors. Methods: Sixty-five chronic stroke survivors and 34 healthy control subjects underwent scanning of the distal radius epiphyseal site on both sides using peripheral quantitative computed tomography to measure trabecular volumetric bone mineral density (vBMD) (mg/cm), total vBMD (mg/cm), total area (mm), and compressive bone strength index (cBSI) (g/cm). Various indicators of neuromuscular (grip strength, spasticity) and cardiovascular function (vascular elasticity, oxygen consumption during 6-min walk test) were evaluated. Results: Analysis of variance revealed a significant main effect of side ( p < 0.001) and group × side interaction ( p < 0.05) for total BMC, total vBMD, trabecular vBMD, and cBSI ( p < 0.05), with the stroke group showing greater side-to-side difference in these variables. However, no significant side-to-side difference in total area was detected in either group ( p > 0.05). Sex-specific analysis yielded similar results. Multiple regression analyses revealed that the cBSI of the hemiparetic distal radius epiphysis had a stronger association with neuromuscular factors than cardiovascular factors. Overall, grip strength was the strongest determinant of the cBSI of the hemiparetic distal radius epiphysis ( p < 0.01). Conclusions: Muscle weakness is the most predominant determinant of cBSI in the hemiparetic distal radius epiphysis among chronic stroke patients. Future studies should investigate the efficacy of different muscle-strengthening strategies in enhancing bone strength of this skeletal site in the chronic stroke population. [ABSTRACT FROM AUTHOR]

The purpose of this study was to identify the determinants of the bone strength index of the distal tibia epiphysis in chronic stroke patients. The results showed that lower cardiovascular fitness, more muscle atrophy, poorer mobility, and more severe spasticity were independently associated with lower tibial bone strength index. To identify the determinants of the bone strength index (BSI) at the distal tibia in chronic stroke patients Sixty-three chronic stroke survivors underwent scanning of the distal tibia at the 4% site on both sides using peripheral quantitative computed tomography. The primary outcomes were trabecular bone mineral density (BMD; milligram per cubic centimeter), total BMD (milligram per cubic centimeter), total bone area (square millimeter), and BSI (square gram per centimeter to the power of four). Cardiovascular fitness, leg lean mass, gait velocity, and spasticity were also measured. Scans from 45 subjects were deemed to have acceptable quality and were included for subsequent analysis. The paretic side had significantly lower trabecular BMD, total BMD, and BSI than the nonparetic side ( p < 0.05). However, the total bone area demonstrated no significant side-to-side difference ( p > 0.05). After adjusting for relevant biological factors, peak oxygen consumption, leg muscle mass, and gait velocity remained positively associated with tibial BSI on both sides ( R2 change = 6.9–14.2%), whereas spasticity of the paretic leg was negatively associated with tibial BSI on the same side ( R2 change = 4.8%). Cardiovascular function, muscle atrophy, mobility, and spasticity are independently associated with BSI of the distal tibia epiphysis among chronic stroke patients. [ABSTRACT FROM AUTHOR]