Adiposity and bone microarchitecture in the GLOW study.

Low body mass index (BMI) is an established risk factor for fractures in postmenopausal women but the interaction of obesity with bone microarchitecture is not fully understood. In this study, obesity was associated with more favourable bone microarchitecture parameters but not after parameters were normalised for body weight. INTRODUCTION: To examine bone microarchitecture in relation to fat mass and examine both areal bone mineral density (aBMD) and microarchitecture in relation to BMI categories in the UK arm of the Global Longitudinal Study of Osteoporosis in Women. METHODS: Four hundred and ninety-one women completed questionnaires detailing medical history; underwent anthropometric assessment; high-resolution peripheral quantitative computed tomography (HRpQCT) scans of the radius and tibia and DXA scans of whole body, proximal femur and lumbar spine. Fat mass index (FMI) residuals (independent of lean mass index) were derived. Linear regression was used to examine HRpQCT and DXA aBMD parameters according to BMI category (unadjusted) and HRpQCT parameters in relation to FMI residuals (with and without adjustment for anthropometric, demographic and lifestyle covariates). RESULTS: Mean (SD) age was 70.9 (5.4) years; 35.0% were overweight, 14.5% class 1 obese and 7.7% class 2/3 obese. There were significant increasing trends according to BMI category in aBMD of whole body, hip, femoral neck and lumbar spine (p ≤ 0.001); cortical area (p < 0.001), thickness (p < 0.001) and volumetric density (p < 0.03), and trabecular number (p < 0.001), volumetric density (p < 0.04) and separation (p < 0.001 for decreasing trend) at the radius and tibia. When normalised for body weight, all HRpQCT and DXA aBMD parameters decreased as BMI increased (p < 0.001). FMI residuals were associated with bone size and trabecular architecture at the radius and tibia, and tibial cortical microarchitecture. CONCLUSION: Significant trends in HRpQCT parameters suggested favourable bone microarchitecture at the radius and tibia with increasing BMI but these were not proportionate to increased weight.

Bone densitometry worldwide: a global survey by the ISCD and IOF.

In a global survey of fracture liaison services, most reported that DXA access met needs. However, adherence to basic DXA quality and reporting procedures was confirmed by only around 50% of institutions and many required education for operators/interpreters. Overall, there is significant variability in the access to, and quality of, DXA services worldwide. INTRODUCTION: While the use of dual-energy X-ray absorptiometry (DXA) has been widely adopted worldwide for the assessment of bone mineral density, the quality of DXA facilities is unknown. To address this, a global survey of fracture liaison services (FLS) was conducted by the International Society for Clinical Densitometry (ISCD) and the International Osteoporosis Foundation (IOF) to assess the quality of their DXA facilities. METHODS: A questionnaire for the accessibility and quality of DXA services was co-created by representatives of the ISCD and the IOF and made available to institutions who participated in the Capture the Fracture Best Practice Framework. From a list of 331 contacted invitees, 124 FLS centres responded; analyses were based on 121 centres with suitable data. RESULTS: Over 70% of institutions reported that, for over 90% of the time, DXA access met service needs, and the scanning/reporting quality was perceived as excellent. However, 25% of DXA facilities reported not being accredited by a professional/governmental organization, and adherence to some basic DXA quality assurance and reporting procedures was confirmed by < 50% of services. Importantly, in excess of 50% of institutions stated that they desired ongoing education in osteoporosis and DXA for operators and interpreters. CONCLUSION: There is significant variability in the access to and quality of DXA services for established FLS worldwide. Despite two decades of training initiatives in osteoporosis densitometry, many centres are falling short of the standards of the IOF-ISCD Osteoporosis Essentials criteria.

Self-perceived Fracture Risk in the Global Longitudinal Study of Osteoporosis in Women: Its Correlates and Relationship with Bone Microarchitecture.

The purpose of this study is to examine correlates of self-perceived fracture risk (SPR) and relationships between SPR and subsequent bone density and microarchitecture in the UK arm of the Global Longitudinal Study of Osteoporosis in Women. 3912 women completed baseline questionnaires detailing medical history and SPR; 492 underwent HRpQCT scans of the radius and tibia and DXA scans of total body, hip, femoral neck and lumbar spine a median of 7.5 years later. Correlates of SPR were examined and a cluster analysis of potential predictors of SPR performed. SPR in relation to HRpQCT and aBMD parameters was examined using linear regression with and without adjustment for anthropometric, demographic and lifestyle covariates. Mean (SD) baseline age was 69.0 (9.0) years; 56.6% reported a similar SPR; 28.6% lower SPR; 14.9% higher SPR compared to women of similar age. In mutually-adjusted analysis, higher SPR was associated (p < 0.05) with: lower physical activity and educational attainment; use of anti-osteoporosis medications (AOM) and calcium supplements; greater number of falls in the previous year; history of fracture since aged 45; family history of hip fracture; and increased comorbidity. Higher SPR, history of fracture, and use of AOM, calcium and vitamin D clustered together. Even after adjustments that included AOM use, higher SPR was associated with: lower radial trabecular volumetric density and number, and higher trabecular separation; lower tibial cortical area and trabecular volumetric density; and lower aBMD at the femoral neck. Despite greater AOM use, women with higher baseline SPR had poorer subsequent bone health.

Relationships between markers of inflammation and bone density: findings from the Hertfordshire Cohort Study.

Among 365 Hertfordshire Cohort Study participants (aged 59-71 years at baseline), higher adiponectin and adiponectin to leptin ratios were associated with lower baseline lumbar spine and femoral neck bone mineral density (BMD). Lower IL-10 was associated with accelerated decline in lumbar spine BMD. This suggests that bone health can be influenced by changes in immune phenotype and alterations in adipokine homeostasis. INTRODUCTION: The aim of this study was to examine the association between indices of inflammation and BMD in a population-based cohort of older adults in the UK. METHODS: Analyses were based on a sample of 194 men and 171 women of the Hertfordshire Cohort Study (community-living, older adults). Dual energy X-ray absorptiometry (DXA) was performed at the lumbar spine and proximal femur at baseline and repeated at a median of 4.5 years (inter-quartile range 3.6 to 5.2). Inflammatory markers (CRP, TNF, IL-1ß, IL-6, IL-8, IL-10, adiponectin and leptin) were ascertained at baseline using enzyme-linked immunosorbent assay (ELISA) techniques and Bio-Plex Pro Assays. Gender-adjusted linear regression was used to examine the associations between markers of inflammation and outcomes with and without adjustment for anthropometric and lifestyle factors. RESULTS: The mean (SD) ages at baseline were 64.4 (2.5) and 66.5 (2.7) years for men and women respectively. Higher levels of adiponectin and adiponectin to leptin ratios were each associated with lower baseline lumbar spine and femoral neck BMD in gender-adjusted (p < 0.01) and fully adjusted (p < 0.05) analyses. Lower levels of IL-10 and TNF were each associated with accelerated decline in lumbar spine BMD in both gender-adjusted (p ≤ 0.05) and fully adjusted (p < 0.05) analyses. CONCLUSIONS: In a cohort of older adults, high levels of adiponectin and adiponectin to leptin ratios were both associated with lower BMD at the lumbar spine and femoral neck at baseline, and lower IL-10 was associated with accelerated decline in BMD at the lumbar spine. This adds weight to the theory that bone health can be influenced by changes in immune phenotype and alterations in adipokine homeostasis.

Bone Phenotype Assessed by HRpQCT and Associations with Fracture Risk in the GLOW Study.

The epidemiology and pathogenesis of fractures in postmenopausal women has previously been investigated in the Global Longitudinal study of Osteoporosis in Women (GLOW). To date, however, relationships between bone imaging outcomes and fracture have not been studied in this cohort. We examined relationships between high-resolution peripheral quantitative computed tomography (HRpQCT) parameters and fracture in the UK arm of GLOW, performing a cluster analysis to assess if our findings were similar to observations reported from older participants of the Hertfordshire Cohort Study (HCS), and extended the analysis to include tibial measurements. We recorded fracture events and performed HRpQCT of the distal radius and tibia and dual-energy X-ray absorptiometry (DXA) of the hip in 321 women, mean age 70.6 (SD 5.4) years, identifying four clusters at each site. We saw differing relationships at the radius and tibia. Two radial clusters (3 and 4) had a significantly lower hip areal bone mineral density (p < 0.001) compared to Cluster 1; only individuals in Cluster 4 had a significantly higher risk of fracture (p = 0.005). At the tibia, clusters 1, 3 and 4 had lower hip areal bone mineral density (p < 0.001) compared to Cluster 2; individuals in Cluster 3 had a significantly higher risk of fracture (p = 0.009). In GLOW our findings at the radius were very similar to those previously reported in the HCS, suggesting that combining variables derived from HRpQCT may give useful information regarding fracture risk in populations where this modality is available. Further data relating to tibial HRpQCT-phenotype and fractures are provided in this paper, and would benefit from validation in other studies. Differences observed may reflect age differences in the two cohorts.

Correlates of Level and Loss of Grip Strength in Later Life: Findings from the English Longitudinal Study of Ageing and the Hertfordshire Cohort Study.

Characterisation of grip strength (GS) using isometric dynamometry is central to the definition of sarcopenia. Determinants of low GS include: older age, shorter stature, low physical activity, poor nutrition, socioeconomic disadvantage and multimorbidity. Less is known about risk factors for accelerated loss of GS. We investigated determinants of level and 8-year loss of GS in 3703 men and women (aged 52-82 years) in the English Longitudinal Study of Ageing (ELSA). Four hundred and forty-one men and women (aged 59-71 years) who participated in a 10-year follow-up of the Hertfordshire Cohort Study (HCS) were used for replication. Variables were harmonised between cohorts. Change in GS was characterised using mixed-effects models in ELSA and a residual change approach in HCS and analysed for men and women combined. Men in ELSA and HCS had higher average levels of GS at baseline, and accelerated rates of loss, compared with women. In ELSA, older age, shorter stature and multimorbidity were correlated with lower level, and accelerated rate of loss, of GS in both sexes (accelerated loss of 0.04 (95% CI 0.00-0.08) standard deviation scores per additional morbidity after multivariable adjustment). Socioeconomic disadvantage, low level of physical activity and poorer self-reported health were also correlated with low GS level, but not loss rate, after multivariable adjustment. Analysis in HCS yielded similar results. Our results identify multimorbidity as a modifiable determinant of loss of muscle strength in later life, and raise the possibility that developmental influences may impact on rate of involutional decline in muscle strength.

Relationships Between Markers of Inflammation and Muscle Mass, Strength and Function: Findings from the Hertfordshire Cohort Study.

We investigated the longitudinal relationships between inflammation markers and the following outcomes in a UK cohort study: appendicular lean mass (ALM); walking speed; level and change in grip strength; and sarcopenia defined by the European Working Group on Sarcopenia in Older People. Analyses were based on 336 community-dwelling older men and women (aged 59-70 years) who participated in the Hertfordshire Cohort Study (HCS). Inflammation markers were ascertained at baseline using enzyme-linked immunosorbent assay techniques and Bio-Plex Pro Assays. Grip strength was measured at baseline and follow-up [median follow-up time: 10.8 years (inter-quartile range 10.2-11.6)] and change in grip strength was ascertained using a residual change approach. At follow-up, ALM was ascertained using dual-energy X-ray absorptiometry, customary walking speed was measured and sarcopenia status was ascertained. Gender-adjusted linear and Poisson regression was used to examine the associations between inflammation markers and outcomes with and without adjustment for anthropometric and lifestyle factors. Higher C-reactive protein was associated (p < 0.04) with lower grip strength and accelerated decline in grip strength from baseline to follow-up. Higher cortisol was associated with lower ALM (p < 0.05). Higher interleukin-8 (IL-8) was associated with lower ALM (p < 0.05) and increased risk of sarcopenia [fully-adjusted relative risk per SD increase in IL-8: 1.37 (95% CI 1.10, 1.71), p = 0.005]. All associations were robust in fully-adjusted analyses. Inflammation markers were associated with measures of muscle mass, strength and function in HCS. Further work is required to replicate these associations and to delineate the underlying mechanisms.

Muscle Mass, Muscle Morphology and Bone Health Among Community-Dwelling Older Men: Findings from the Hertfordshire Sarcopenia Study (HSS).

Sarcopenia and osteoporosis are associated with poor health outcomes in older people. Relationships between muscle and bone have typically been reported at a functional or macroscopic level. The aims of this study were to describe the relationships between muscle morphology and bone health among participants of the Hertfordshire Sarcopenia Study (HSS). 105 older men, mean age 72.5 (SD 2.5) years, were recruited into the HSS. Whole body lean mass as well as appendicular lean mass, lumbar spine and femoral neck bone mineral content (BMC) and bone mineral density (BMD) were obtained through dual-energy X-ray absorptiometry scanning. Percutaneous biopsy of the vastus lateralis was performed successfully in 99 participants. Image analysis was used to determine the muscle morphology variables of slow-twitch (type I) and fast-twitch (type II) myofibre area, myofibre density, capillary and satellite cell (SC) density. There were strong relationships between whole and appendicular lean body mass in relation to femoral neck BMC and BMD (r ≥ 0.43, p < 0.001). Type II fibre area was associated with both femoral neck BMC (r = 0.27, p = 0.01) and BMD (r = 0.26, p = 0.01) with relationships robust to adjustment for age and height. In unadjusted analysis, SC density was associated with whole body area (r = 0.30, p = 0.011) and both BMC (r = 0.26, p = 0.031) and area (r = 0.29, p = 0.017) of the femoral neck. We have demonstrated associations between BMC and changes in muscle at a cellular level predominantly involving type II myofibres. Interventions targeted at improving muscle mass, function and quality may improve overall musculoskeletal health. Larger studies that include women are needed to explore these relationships further.

Skeletal muscle morphology in sarcopenia defined using the EWGSOP criteria: findings from the Hertfordshire Sarcopenia Study (HSS).

BACKGROUND: Sarcopenia is defined as the loss of muscle mass and function with age and is associated with decline in mobility, frailty, falls and mortality. There is considerable interest in understanding the underlying mechanisms. Our aim was to characterise muscle morphology changes associated with sarcopenia among community dwelling older men. METHODS: One hundred and five men aged 68-76 years were recruited to the Hertfordshire Sarcopenia Study (HSS) for detailed characterisation of muscle including measures of muscle mass, strength and function. Muscle tissue was obtained from a biopsy of the vastus lateralis for 99 men and was processed for immunohistochemical studies to determine myofibre distribution and area, capillarisation and satellite cell (SC) density. RESULTS: Six (6 %) men had sarcopenia as defined by the European Working Group on Sarcopenia in Older People (EWGSOP) criteria. These men had lower SC density (1.7 cells/mm(2) vs 3.8 cells/mm(2), p = 0.06) and lower SC/fibre ratio (0.02 vs 0.06, p = 0.06) than men without sarcopenia. Although men with sarcopenia tended to have smaller myofibres and lower capillary to fibre ratio, these relationships were not statistically significant. CONCLUSION: We have shown that there may be altered muscle morphology parameters in older men with sarcopenia. These results have the potential to help identify cell and molecular targets for therapeutic intervention. This work now requires extension to larger studies which also include women.

Minocycline-induced intraoral pharmacogenic pigmentation: case reports and review of the literature.

Minocycline, a semi-synthetic tetracycline antibiotic, is well documented as being associated with pharmacogenic pigmentation of various tissues in humans and other mammals. The most obvious of these are skin pigmentation, but intraorally include "green" roots of erupted teeth, "black" roots of extracted teeth, a dark stain of the crowns of fully developed teeth, and "black" alveolar bone. This article presents five cases of "black" alveolar bone with photographic documentation of its progress. It also reviews the available English language literature on this phenomenon. The incidence of minocycline staining of alveolar bone is probably 2% of that population taking the drug for 2 months or longer. Presently, minocycline is most widely used in the young adult population for the treatment of acne. With the recent interest in minocycline as a palliative treatment for rheumatiod arthritis, an entirely different population could be experiencing this effect. If minocycline use becomes widespread as a treatment for rheumatoid arthritis, it is likely that more practitioners will be asked to diagnose this sometimes striking, though apparently benign, condition. Recognition of this condition will save the practitioner and the patient from unnecessary concern and surgery.

Dentin matrix gelatin (DMG) as a possible "universal" grafting material in periodontics.

The ideal of periodontal surgery is the total regeneration of the lost periodontal complex. A promising new osseous grafting material is Dental Matrix Gelation (DMG). DMG was prepared by a method similar to that of Conover and Urist (1979). This consisted of sequential extraction in 1:1 chloroform-methanol, 25 degrees C for 1 hour; 0.6 N HCl, 2 degrees C for 24 hours with constant agitation; 2 M CaCl2, 2 degrees C for 1 hour; 0.5 M EDTA pH 7.4, 2 degrees C for 1 hour; washed in distilled water 1 hour. Twelve rats were anesthetized, had heads shaved, midline flaps reflected, and 2 mm holes drilled through the right and left parietal bones. This type of osseous defect normally heals only by fibrous scarring and has been used to define osteoinductive materials. The DMG was cut into pieces about 1 mm square and placed into the right side defect while the left side remained open as a control. The animals were sacrificed on a schedule of two rats every 2 weeks until the 10th week when four rats were killed. The results showed complete osseous closure of the DMG site while the control healed by fibrous scarring. DMG seems to have strong osteoinductive power, and used allogenically has great potential as a commercially viable implant material.

Ultrastructural study of the attachment of human gingiva to titanium in vivo.

A study was conducted to determine if the behavior of epithelium in vitro is similar to its attachment behavior in vivo by the use of small sections of titanium-coated implants that could be inserted in human gingiva. The size of the implants allowed their insertion in a limited region and enabled the fixation and embedding procedures that are necessary for electron microscopy to be effective. Examination of the thin sections obtained from this material demonstrated that the epithelial cells attached to titanium in a manner similar to that observed in vitro and similar to the way that epithelium attaches to the tooth in vivo (Fig. 2). That is, there was a formation of hemidesmosomes and basal lamina. Because the ability of the oral epithelium to form such an attachment with an implant may be a crucial factor in the determination of clinical success or failure, this study provides further evidence that one reason for the apparent clinical success of titanium dental implants may lie in the firm attachment of epithelial cells to this material.

Arm ergometry exercise testing in patients with dysvascular amputations.

The purpose of this study was to test the agreement between the heart rate (HR) response and rating of perceived exertion (RPE) on an arm ergometry graded exercise test (GXT) in deconditioned persons with acute dysvascular amputations before and after an inpatient rehabilitation program. Twenty-six men were studied at admission, and 11 were retested after completion of the program. After obtaining resting measurements of HR and systolic and diastolic blood pressures, each patient performed the GXT using an arm ergometer. Patients maintained a cranking rate of 50rpm, which was monitored electronically. The workloads started with a warm-up period of 0 watts (stage 1) and increased by increments of 5 watts. Each stage lasted three minutes-2.5 minutes of exercise and 30 seconds of rest. The RPE was taken five seconds before the end of each exercise stage. During the rest period, HR and blood pressures were recorded. Scatter plots and linear regression analyses revealed no statistically significant relationship, either at early stages of GXT or at peak work, between HR and RPE. The results suggest that RPE cannot be used reliably as a surrogate for direct pulse measurement in exercise training of persons with acute dysvascular amputations.

Exercise testing and training of persons with dysvascular amputation: safety and efficacy of arm ergometry.

Recent studies indicate that most persons with dysvascular amputation also have moderate to severe cardiovascular disease with impairment in functional capacity. This may limit the ability to achieve optimal function with their prosthesis because of inadequate conditioning. We developed an exercise testing and training program using arm ergometry in conjunction with standard rehabilitation for persons with acute dysvascular amputation who were profoundly deconditioned after complicated perioperative courses. The program consisted of daily arm ergometry, performed on an interval basis, at an intensity individually optimized through exercise testing. Twenty-five patients, with a mean age of 63 years, completed the inpatient program with pretest and discharge work performance assessment. There was no significant difference between pretest and discharge assessment of baseline or peak heart rate, systolic blood pressure, diastolic blood pressure, or Borg rating of perceived exertion. Peak systolic blood pressure was elevated at discharge compared to admission testing (p less than .04). Heart rate responses were decreased during the early stages of testing when comparing discharge telemetry to admission findings. The duration of exercise increased from 12.6 minutes to 16.3 minutes (p less than .0004), and the maximum work output increased from 17.1 watts to 23.5 watts (p less than .0004). There was no significant morbidity associated with either arm ergometry testing or the exercise program. We conclude that arm ergometry testing and training is a safe and effective method for improving the efficiency of arm work in the patient with acute dysvascular amputation.