The good, the bad and the ugly of bone-anchored prostheses: Guideline to assess true clinical outcomes

The aim of this study is to share the key elements of an evaluation framework to determine the true clinical outcomes of bone-anchored prostheses. Scientists, clinicians and policy makers are encouraged to implement their own evaluations relying on the proposed framework using a single database to facilitate reflective practice and, eventually, robust prospective studies.

Vascular calcification and mineral bone disorder in chronic kidney disease

Chronic Kidney Disease (CKD), osteoporosis and mild hyponatremia are all prevalent chronic conditions that may coexist and are often under-recognized. Mineral-Bone Disorder begins early in the natural history of CKD and results in complex abnormalities of bone which ultimately confers a well-established increased risk of fragility fractures in End Stage Kidney Disease. Hyponatremia is a novel, usually renal mediated metabolic perturbation, that most commonly occurs independently of the stage of renal dysfunction but which may also predispose to increased fracture risk. The extent -if any- to which either early stages of renal dysfunction or the presence of hyponatremia contribute to fracture occurrence in the general population, independently of osteoporosis, is unclear. Renal transplantation is the treatment of choice for ESKD and although it restores endogenous renal function it typically fails to normalize either the long term cardiovascular or fracture risk. One potential mechanism contributing to these elevated long-term risks and to diminished Health Related Quality of Life is persistent, post-transplant hyperparathyroidism. In this study we retrospectively examine the association of renal function and serum sodium with Bone Mineral Density and fracture occurrence in a retrospective cohort of 1930 female members of the general population who underwent routine DXA scan. We then prospectively recruited a cohort of 90 renal transplant recipients in order to examine the association of post transplant parathyroid hormone (PTH) level with measures of CKD Mineral Bone Disorder, including, DXA Bone Mineral Density, Vascular Calcification (assessed using both abdominal radiography and CT techniques, as well as indirectly by carotid-femoral Pulse Wave Velocity) and Quality of Life (using the Short Form-12 and a PTH specific symptom score). In the retrospective DXA cohort, moderate CKD (eGFR 30-59ml/min/1.73m2) and hyponatremia (<135mmol/L) were associated with fracture occurrence, independently of BMD, with an adjusted Odds Ratio (95% Confidence Interval), of 1.37 (1.0, 1.89) and 2.25 (1.24, 4.09) respectively. In the renal transplant study, PTH was independently associated with the presence of osteoporosis, adjusted Odds Ratio (95% Confidence Interval), 1.15 (per 10ng/ml increment), (1.04, 1.26). The presence of osteoporosis but not PTH was independently associated with measures of vascular calcification, adjusted ß (95% Confidence Interval), 12.45, (1.16, 23.75). Of the eight quality-of-life domains examined, post-transplant PTH (per 10ng/ml increment), was only significantly and independently associated with reduced Physical Functioning, (95% Confidence Interval), 1.12 (1.01, 1.23). CKD and hyponatremia are both common health problems that may contribute to fracture occurrence in the general population, a major on-going public health concern. PTH and decreased Bone Mineral Density may signal sub-optimal long-term outcomes post renal transplantation, influencing bone and vascular health and to a limited extent long term Health Related Quality of Life

Fluoridation for dental public health

This article reviews the means by which fluoride is supplied to populations. Many public health authorities provide fluoridated drinking water, with typical concentrations of fluoride of between 0.5 and 1.0 ppm. This has been found to be safe and effective, though differences in caries incidence between fluoridated and non-fluoridated regions are less than they were 50 years ago, because of the wider availability of fluoridated products to the whole population. Concerns about the effect of fluoride on bone density and associated conditions are reviewed and the general conclusion from considering the literature on fluoride is that there is almost no cause for concern. Alternatives to water as a means of delivering fluoride to the general public that are being used in a number of countries are salt and milk. These alternatives are also reviewed and have been shown to give satisfactory levels of protection against caries, though milk is shown to be less satisfactory than water as a vehicle for fluoride delivery. Milk is also less effective in providing fluoride to individuals in the population, and is less likely to be consumed by people in lower socio-economic groups, precisely those who suffer most from dental caries. This study concludes that mass water fluoridation remains an important contribution to good oral health throughout the community.

Neuropeptide Y (NPY) and NPY Y1 receptor in periodontal health and disease

Abstract
OBJECTIVES:
Neuropeptide Y (NPY) coordinates inflammation and bone metabolism which are central to the pathogenesis of periodontitis. The present study was designed to determine whether NPY was quantifiable in human gingival crevicular fluid (GCF) and to test the null hypothesis that GCF levels of NPY were the same in periodontal health and disease. A subsidiary aim was to determine the potential functionality of released NPY by detecting the presence of NPY Y1 receptors in gingival tissue.
DESIGN:
The periodontitis group consisted of 20 subjects (10 females and 10 males) mean age 41.4 (S.D. 9.6 years). The control group comprised 20 subjects (10 females and 10 males) mean age 37.4 (S.D. 11.7 years). NPY levels in GCF were measured in periodontal health and disease by radioimmunoassay. NPY Y1 receptor expression in gingival tissue was determined by Western blotting of membrane protein extracts from healthy and inflamed gum.
RESULTS:
Healthy sites from control subjects had significantly higher levels of NPY than diseased sites from periodontitis subjects. NPY Y1 receptor protein was detected in both healthy and inflamed gingival tissue by Western blotting.
CONCLUSIONS:
The significantly elevated levels of NPY in GCF from healthy compared with periodontitis sites suggests a tonic role for NPY, the functionality of which is indicated by the presence of NPY Y1 receptors in local gingival tissue.

Bone mineral density in relation to medical and lifestyle risk factors for osteoporosis in premenopausal, menopausal and postmenopausal women in general practice

Background: Interest in the prevention of osteoporosis is increasing and thus there is a need for an acceptable osteoporosis prevention programme in general practice. AIM. A study was undertaken to identify a cohort of middle-aged women attending a general practice who would be eligible for a longitudinal study looking at bone mineral density, osteoporosis and the effectiveness of hormone replacement therapy. This study aimed to describe the relationship between medical and lifestyle risk factors for osteoporosis and the initial bone density measurements in this group of women. METHOD. A health visitor administered a questionnaire to women aged between 48 and 52 years registered with a Belfast general practice. The main outcome measures were menopausal status, presence of medical and lifestyle risk factors and bone mineral density measurements. RESULTS. A total of 358 women our of 472 (76%) took part in the study which was conducted in 1991 and 1992. A highly significant difference was found between the mean bone mineral density of premenopausal, menopausal and postmenopausal women within the narrow study age range, postmenopausal women having the lowest bone mineral density. A significant relationship was found between body mass index and bone mineral density, a greater bone mineral density being found among women with a higher body mass index. Risk factors such as smoking and sedentary lifestyle were common (reported by approximately one third of respondents) but a poor relationship was found between these two and all the other risk factors and bone mineral density in this age group. CONCLUSION. Risk of osteoporosis cannot be identified by the presence of risk factors in women aged between 48 and 52 years. In terms of a current prevention strategy for general practice it would be better to take a population-based approach except for those women known to be at high risk of osteoporosis: women with early menopause or those who have had an oophorectomy.

Management of Hyperphosphataemia in Chronic Kidney Disease:Summary of National Institute for Health and Clinical Excellence (NICE) Guideline

Bone disease and ectopic calcification are the two main consequences of hyperphosphataemia of chronic kidney disease (CKD). Observational studies have demonstrated that hyperphosphataemia in CKD is associated with increased mortality. Furthermore, the use of phosphate binders in dialysis patients is associated with significantly lower mortality. The UK Renal Registry data show significant underachievement of phosphate targets in dialysis patients. It is believed to be due to wide variation in how management interventions are used. The National Institute for Health and Clinical Excellence (NICE) has developed a guideline on the management of hyperphosphataemia in CKD. This is based on the evidence currently available using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. This review outlines the recommendations including research recommendations and discusses methodology, rationale and challenges faced in developing this guideline and the health economic model used to assess the cost-effectiveness of different phosphate binders. © 2013 S. Karger AG, Basel.

Physical Stature Decline and the Health Status of the Elderly Population in England

Few research papers in economics have examined the extent, causes or consequences of physical stature decline in aging populations. Using repeated observations on objectively measured data from the English Longitudinal Study of Ageing (ELSA), we document that reduction in height is an important phenomenon among respondents aged 50 and over. On average, physical stature decline occurs at an annual rate of between 0.08% and 0.10% for males, and 0.12% and 0.14% for females—which approximately translates into a 2cm to 4cm reduction in height over the life course. Since height is commonly used as a measure of long-run health, our results demonstrate that failing to take age-related height loss into account substantially overstates the health advantage of younger birth cohorts relative to their older counterparts. We also show that there is an absence of consistent predictors of physical stature decline at the individual level. However, we demonstrate how deteriorating health and reductions in height occur simultaneously. We document that declines in muscle mass and bone density are likely to be the mechanism through which these effects are operating. If this physical stature decline is determined by deteriorating health in adulthood, the coefficient on measured height when used as an input in a typical empirical health production function will be affected by reverse causality. While our analysis details the inherent difficulties associated with measuring height in older populations, we do not find that significant bias arises in typical empirical health production functions from the use of height which has not been adjusted for physical stature decline. Therefore, our results validate the use of height among the population aged over 50.

Aging impairs peritoneal but not bone marrow-derived macrophage phagocytosis

Aging results in deterioration of the immune system, which is associated with increased susceptibility to infection and impaired wound healing in the elderly. Phagocytosis is an essential process in both wound healing and immune defence. As such, age-related impairments in phagocytosis impact on the health of the elderly population. Phagocytic efficiency in peritoneal macrophages, bone marrow-derived macrophages and bone marrow monocytes from young and old mice was investigated. Aging significantly impaired phagocytosis by peritoneal macrophages, both in vitro and in vivo. However, bone marrow-derived macrophages and bone marrow monocytes did not exhibit age-related impairments in phagocytosis, suggesting no intrinsic defect in these cells. We sought to investigate underlying mechanisms in age-related impairments in phagocytosis by peritoneal macrophages. We hypothesized that microenvironmental factors in the peritoneum of old mice impaired macrophage phagocytosis. Indeed, macrophages from young mice injected into the peritoneum of old mice exhibited impaired phagocytosis. Proportions of peritoneal immune cells were characterized, and striking increases in numbers of T cells, B1 and B2 cells were observed in the peritoneum of old mice compared with young mice. In addition, B cell-derived IL-10 was increased in resting and LPS-activated peritoneal cell cultures from old mice. These data demonstrate that aging impairs phagocytosis by tissue-resident peritoneal macrophages, but not by bone marrow-derived macrophages/monocytes, and suggest that age-related defects in macrophage phagocytosis may be due to extrinsic factors in the tissue microenvironment. As such, defects may be reversible and macrophages could be targeted therapeutically in order to boost immune function in the elderly.

The TORCH (towards a revolution in COPD health) survival study protocol

Only long-term home oxygen therapy has been shown in randomised controlled trials to increase survival in chronic obstructive pulmonary disease (COPD). There have been no trials assessing the effect of inhaled corticosteroids and long-acting bronchodilators, alone or in combination, on mortality in patients with COPD, despite their known benefit in reducing symptoms and exacerbations. The "TOwards a Revolution in COPD Health" (TORCH) survival study is aiming to determine the impact of salmeterol/fluticasone propionate (SFC) combination and the individual components on the survival of COPD patients. TORCH is a multicentre, randomised, double-blind, parallel-group, placebo-controlled study. Approximately 6,200 patients with moderate-to-severe COPD were randomly assigned to b.i.d. treatment with either SFC (50/500 microg), fluticasone propionate (500 microg), salmeterol (50 microg) or placebo for 3 yrs. The primary end-point is all-cause mortality; secondary end-points are COPD morbidity relating to rate of exacerbations and health status, using the St George's Respiratory Questionnaire. Other end-points include other mortality and exacerbation end-points, requirement for long-term oxygen therapy, and clinic lung function. Safety end-points include adverse events, with additional information on bone fractures. The first patient was recruited in September 2000 and results should be available in 2006. This paper describes the "TOwards a Revolution in COPD Health" study and explains the rationale behind it.

In postmenopausal women with osteoporosis, denosumab significantly improved trabecular bone score (TBS), an index of trabecular microarchitecture

Background/Purpose: The trabecular bone score (TBS), a novel graylevel texture index determined from lumbar spine DXA scans, correlates with 3D parameters of trabecular bone microarchitecture known to predict fracture. TBS may enhance the identification of patients at increased risk for vertebral fracture independently of bone mineral density (BMD) (Boutroy JBMR 2010; Hans JBMR 2011). Denosumab treatment for 36 months decreased bone turnover, increased BMD, and reduced new vertebral fractures in postmenopausal women with osteoporosis (Cummings NEJM 2009). We explored the effect of denosumab on TBS over 36 months and evaluated the association between TBS and lumbar spine BMD in women who had DXA scans obtained from eligible scanners for TBS evaluation in FREEDOM. Methods: FREEDOM was a 3-year, randomized, double-blind trial that enrolled postmenopausal women with a lumbar spine or total hip DXA T-score __2.5, but not __4.0 at both sites. Women received placebo or 60 mg denosumab every 6 months. A subset of women in FREEDOM participated in a DXA substudy where lumbar spine DXA scans were obtained at baseline and months 1, 6, 12, 24, and 36. We retrospectively applied, in a blinded-to-treatment manner, a novel software program (TBS iNsightR v1.9, Med-Imaps, Pessac, France) to the standard lumbar spine DXA scans obtained in these women to determine their TBS indices at baseline and months 12, 24, and 36. From previous studies, a TBS _1.35 is considered as normal microarchitecture, a TBS between 1.35 and _1.20 as partially deteriorated, and 1.20 reflects degraded microarchitecture. Results: There were 285 women (128 placebo, 157 denosumab) with a TBS value at baseline and _1 post-baseline visit. Their mean age was 73, their mean lumbar spine BMD T-score was _2.79, and their mean lumbar spine TBS was 1.20. In addition to the robust gains in DXA lumbar spine BMD observed with denosumab (9.8% at month 36), there were consistent, progressive, and significant increases in TBS compared with placebo and baseline (Table & Figure). BMD explained a very small fraction of the variance in TBS at baseline (r2_0.07). In addition, the variance in the TBS change was largely unrelated to BMD change, whether expressed in absolute or percentage changes, regardless of treatment, throughout the study (all r2_0.06); indicating that TBS provides distinct information, independently of BMD. Conclusion: In postmenopausal women with osteoporosis, denosumab significantly improved TBS, an index of lumbar spine trabecular microarchitecture, independently of BMD.

Effects of dietary restraint and oral contraceptives on bone strength and bone turnover in young women

ABSTRACT Introduction The purpose of this study was to assess specific osteoporosis-related health behaviours and physiological outcomes including daily calcium intake, physical activity levels, bone strength, as assessed by quantitative ultrasound, and bone turnover among women between the ages of 18 and 25. Respective differences on relevant study variables, based on dietary restraint and oral contraceptive use were also examined. Methods One hundred women (20.6 ± 0.2 years of age) volunteered to participate in the study. Informed written consent was obtained by all subjects prior to participation. The study and all related procedures were approved by the Brock University Research Ethics Board. Body mass, height, relative body fat, as well as chest, waist and hip circumferences were measured using standard procedures. The 10-item restrained eating subscale of the Dutch Eating Behaviour Questionnaire (DEBQ) was used to assess dietary restraint (van Strien et al., 1986). Daily calcium intake was assessed by the Rapid Assessment Method (RAM) (Hertzler & Frary 1994). Weekly physical activity was documented by the 4-item Godin Leisure-Time Exercise Questionnaire (Godin & Shephard 1985). Bone strength was determined from the speed of sound (SOS) as measured by QUS (Sunlight 7000S). SOS measurements (m/s) were taken of the dominant and non-dominant sides of the distal one third of the radius and the mid-shaft of the tibia. Resting blood samples were collected from all subjects between 9am and 12pm, in order to evaluate the impact of lifestyle factors on biochemical markers of bone turnover. Blood was collected during the early follicular phase of the menstrual cycle (approximately days 1-5) for all subjects. Samples were centrifliged and the serum or plasma was aliquoted into separate tubes and stored at -80°C until analysis. The bone formation markers measured were Osteocalcin (OC), bone specific alkaline phosphatase (BAP) and 25-OH vitamin D. The bone resorption markers measured were the carboxy (CTx) and amino (NTx) terminal telopeptides of type-I collagen crosslinks. All markers were assessed by ELISA. Subjects were divided into high (HDR) and low dietary restrainers (LDR) based on the median DEBQ score, and also into users (BC) and non-users (nBC) of oral contraceptives. A series of multiple one way ANOVA's were then conducted to identify differences between each set of groups for all relevant variables. A two-way ANOVA analysis was used to explore significant interactions between dietary restraint and use of oral contraceptives while a univariate follow-up analysis was also performed when appropriate. Pearson Product Moment Correlations were used to determine relationships among study variables. Results HDR had significantly higher BMI, %BF and circumference measures but lower daily calcium intake than LDR. There were no significant differences in physical activity levels between HDR and LDR. No significant differences were found between BC and nBC in body composition, calcium intake and physical activity. HDR had significantly lower tibial SOS scores than LDR in both the dominant and non-dominant sites. The post-hoc analysis showed that within the non-birth control group, the HDR had significantly lower tibial SOS scores of bone strength when compared to the LDR but Aere were no significant differences found between the two dietary restraint groups for those currently on birth control. HDR had significantly lower levels of OC than LDR and the BC group had lower levels of BAP than the nBC group. Consistently, the follow-up analysis revealed that within those not on birth control, subjects who were classified as HDR had significantly (f*<0.05) lower levels of OC when compared with LDR but no significant differences were observed in bone turnover between the two dietary restraint groups for those currently on birth control. Physical activity was not correlated with SOS scores and bone turnover markers possibly due to the low physical activity variability in this group of women. Conclusion This is the first study to examine the effects of dietary restraint on bone strength and turnover among this population of women. The most important finding of this study was that bone strength and turnover are negatively influenced by dietary restraint independent of relative body fat. In general, the results of the present thesis suggest that dietary restraint, oral contraceptive use, as well as low daily calcium intake and low physical activity levels were widespread behaviours among this population of college-aged women. The young women who were using dietary restraint as a strategy to lose weight, and thus were in the HDR group, despite their higher relative body fat and weight, had lower scores of bone strength and lower levels of markers of bone turnover compared to the low dietary restrainers. Additionally, bone turnover seemed to be negatively affected by oral contraceptives, while bone strength, as assessed by QUS, seemed unaffected by their use in this population of young women. Physical activity (weekly energy expenditure), on the other hand, was not associated with either bone strength or bone tiimover possibly due to the low variability of this variable in this population of young Canadian women.

Bone speed of sound, biochemical markers of bone turnover and IGF-1 in competetive synchronized swimmers

The purpose of this study was to compare bone speed of sound (SOS) measured by quantitative ultrasound, circulating levels of IGF- 1 and biochemical markers of bone turnover in pre- (Pr) and post-menarcheal (Po) synchronized swimmers (SS) and controls (NS). Seventy participants were recruited: 8 PrSS, 22 PoSS, 20 PrNS, and 20 PoNS. Anthropometric measures of height, weight, skeletal maturity and percent body fat were taken, and dietary intake evaluated using 24-hour recall. Bone SOS was measured at the distal radius and mid-tibia and blood samples analyzed for IGF-1, osteocalcin, NTx, and 25-OH vitamin D. Results demonstrated maturational effects on bone SOS, IGF-1 and bone turnover (p<0.05), with no differences observed between SS and NS. Main effects were observed for a reduced caloric intake in SS compared to NS (p<0.05). Therefore, SS does not offer additive affects on bone strength but imparts no adverse affects to skeletal health in these athletes.

Bone speed of sound in overweight and normal-weight girls and adolescents

Over the last two decades, the prevalence of obesity in the general population has been steadily increasing. Obesity is a major issue in scientific research because it is associated with many health problems, one of which is bone quality. In adult females, adiposity is associated with increased bone mineral density, suggesting that there is a protective effect of fat on bone. However, the association between adiposity and bone strength during childhood is not clear. Thus, the purpose of this study was to compare bone strength, as reflected by speed of sound (SOS), of overweight and obese girls and adolescents with normal-weight age-matched controls. Data from 75 females included normal-weight girls (G-NW; body fat:::; 25%; n = 21), overweight and obese girls (GOW; body fat ~ 28%; n = 19), normal-weight adolescents (A-NW, body fat:::; 25%; n = 13) and overweight and obese adolescents (A-OW; body fat ~ 28%; n = 22). Nutrition was assessed with a 24-hour recall questionnaire and habitual physical activity was measured for one week using accelerometry. Using quantitative ultrasound (QUS; Sunlight Omnisense™), bone SOS was measured at the distal radius and mid-tibia. No differences were found between groups in daily total energy, calcium or vitamin D intake. However, all groups were below the recommended daily calcium intake of 1300 mg (Osteoporosis Canada, 2008). Adolescents were significantly less active than girls (14.7 ± 0.6 vs. 6.3 ± 0.6% active for G and A, respectively). OW accumulated significantly less minutes of moderate-to-very vigorous physical activity per day (MVPA) than NW in both age groups (114 ± 6 vs. 57 ± 5 min/day for NW and OW, i respectively). Girls had significantly lower radial SOS (3794 ± 87 vs. 3964 ± 64 mls for G-NW and A-NW, respectively), and tibial SOS (3678 ± 86 vs. 3878 ± 52 mls for G-NW and A-NW, respectively) than adolescents. Radial SOS was similar in the two adiposity groups within each age group. However, tibial SOS was lower in the two overweight groups (3601 ± 75 mls vs. 3739 ± 134 mls for G-OW and A-OW, respectively) compared with the age-matched normal-weight controls. Body fat percentage negatively correlated with tibial SOS in the study sample as a whole (r = -0.30). However, when split into groups, percent bo~y fat correlated with tibial SOS only in the A-OW group (r = -0.53). MVPA correlated with tibial SOS (r = 0.40), once age was partialed out. In conclusion, in contrast withthe higher bone strength characteristic of obese adult women, overweight and obese girls and adolescents are characterized by low tibial bone strength, as assessed with QUS. The differences between adiposity groups in tibial SOS may be at least partially due to the reduced weight-bearing physical activity levels in the overweight girls and adolescents. However, other factors, such as hormonal influences associated with high body fat may also playa role in reducing bone strength in overweight girls. Further research is required to reveal the mechanisms causing low bone strength in overweight and obese children and adolescents.

Relative importance of body composition, osteoporosis- related behaviours and socioeconomic status on bone SOS in adolescent females

The purpose of this study was to examine the associations between bone speed of sound (SOS) and body composition, osteoporosis-related health behaviours, and socioeconomic status (SES) in adolescent females. A total of 442 adolescent females in grades 9-11 participated. Anthropometric measures of height, body mass, and percent body fat were taken, and osteo-protective behaviours such as oral contraceptive use (OC), physical activity and daily calcium intake were evaluated using self-report questionnaires. Bone SOS was measured by transaxial quantitative ultrasound (QUS) at the distal radius and mid-tibia. The results suggest that fat mass is a significant negative predictor of tibial SOS, while lean mass is positively associated with radial SOS scores and calcium intake was positively associated with tibial SOS scores (pbone SOS. Therefore bone strength measured by QUS is reduced in adolescents with an increased fat mass, and influenced positively by OC use, calcium intake and lean mass.