Showing papers in "Osteoporosis International in 2016"

The National Osteoporosis Foundation’s position statement on peak bone mass development and lifestyle factors: a systematic review and implementation recommendations

Abstract: Lifestyle choices influence 20–40 % of adult peak bone mass. Therefore, optimization of lifestyle factors known to influence peak bone mass and strength is an important strategy aimed at reducing risk of osteoporosis or low bone mass later in life. The National Osteoporosis Foundation has issued this scientific statement to provide evidence-based guidance and a national implementation strategy for the purpose of helping individuals achieve maximal peak bone mass early in life. In this scientific statement, we (1) report the results of an evidence-based review of the literature since 2000 on factors that influence achieving the full genetic potential for skeletal mass; (2) recommend lifestyle choices that promote maximal bone health throughout the lifespan; (3) outline a research agenda to address current gaps; and (4) identify implementation strategies. We conducted a systematic review of the role of individual nutrients, food patterns, special issues, contraceptives, and physical activity on bone mass and strength development in youth. An evidence grading system was applied to describe the strength of available evidence on these individual modifiable lifestyle factors that may (or may not) influence the development of peak bone mass (Table 1). A summary of the grades for each of these factors is given below. We describe the underpinning biology of these relationships as well as other factors for which a systematic review approach was not possible. Articles published since 2000, all of which followed the report by Heaney et al. [1] published in that year, were considered for this scientific statement. This current review is a systematic update of the previous review conducted by the National Osteoporosis Foundation [1]. Considering the evidence-based literature review, we recommend lifestyle choices that promote maximal bone health from childhood through young to late adolescence and outline a research agenda to address current gaps in knowledge. The best evidence (grade A) is available for positive effects of calcium intake and physical activity, especially during the late childhood and peripubertal years—a critical period for bone accretion. Good evidence is also available for a role of vitamin D and dairy consumption and a detriment of DMPA injections. However, more rigorous trial data on many other lifestyle choices are needed and this need is outlined in our research agenda. Implementation strategies for lifestyle modifications to promote development of peak bone mass and strength within one’s genetic potential require a multisectored (i.e., family, schools, healthcare systems) approach.

Calcium plus vitamin D supplementation and risk of fractures: an updated meta-analysis from the National Osteoporosis Foundation

Abstract: The aim was to meta-analyze randomized controlled trials of calcium plus vitamin D supplementation and fracture prevention. Meta-analysis showed a significant 15 % reduced risk of total fractures (summary relative risk estimate [SRRE], 0.85; 95 % confidence interval [CI], 0.73–0.98) and a 30 % reduced risk of hip fractures (SRRE, 0.70; 95 % CI, 0.56–0.87). Calcium plus vitamin D supplementation has been widely recommended to prevent osteoporosis and subsequent fractures; however, considerable controversy exists regarding the association of such supplementation and fracture risk. The aim was to conduct a meta-analysis of randomized controlled trials [RCTs] of calcium plus vitamin D supplementation and fracture prevention in adults. A PubMed literature search was conducted for the period from July 1, 2011 through July 31, 2015. RCTs reporting the effect of calcium plus vitamin D supplementation on fracture incidence were selected from English-language studies. Qualitative and quantitative information was extracted; random-effects meta-analyses were conducted to generate summary relative risk estimates (SRREs) for total and hip fractures. Statistical heterogeneity was assessed using Cochran’s Q test and the I 2 statistic, and potential for publication bias was assessed. Of the citations retrieved, eight studies including 30,970 participants met criteria for inclusion in the primary analysis, reporting 195 hip fractures and 2231 total fractures. Meta-analysis of all studies showed that calcium plus vitamin D supplementation produced a statistically significant 15 % reduced risk of total fractures (SRRE, 0.85; 95 % confidence interval [CI], 0.73–0.98) and a 30 % reduced risk of hip fractures (SRRE, 0.70; 95 % CI, 0.56–0.87). Numerous sensitivity and subgroup analyses produced similar summary associations. A limitation is that this study utilized data from subgroup analysis of the Women’s Health Initiative. This meta-analysis of RCTs supports the use of calcium plus vitamin D supplements as an intervention for fracture risk reduction in both community-dwelling and institutionalized middle-aged to older adults.

Age-associated declines in muscle mass, strength, power, and physical performance: impact on fear of falling and quality of life

Abstract: Summary This 3-year longitudinal study among older adults showed that declining muscle mass, strength, power, and physical performance are independent contributing factors to increased fear of falling, while declines of muscle mass and physical performance contribute to deterioration of quality of life. Our findings reinforce the importance of preserving muscle health with advancing age.

Impact of hip fracture on hospital care costs: a population-based study

Abstract: Summary Using a large cohort of hip fracture patients, we estimated hospital costs to be £14,163 and £2139 in the first and second year following fracture, respectively. Second hip and non-hip fractures were major cost drivers. There is a strong economic incentive to identify cost-effective approaches for hip fracture prevention.

Proton-pump inhibitors and risk of fractures: an update meta-analysis

Abstract: To identify the relationship between proton-pump inhibitors (PPIs) and the risk of fracture, we conducted an update meta-analysis of observational studies. Results showed that PPI use was associated with a modestly increased risk of hip, spine, and any-site fracture. Many studies have investigated the association of proton-pump inhibitors (PPIs) with fracture risk, but the results have been inconsistent. To evaluate this question, we performed a meta-analysis of relevant observational studies. A systematic literature search up to February 2015 was performed in PubMed. We combined relative risks (RRs) for fractures using random-effects models and conducted subgroup and stratified analyses. Eighteen studies involving a total of 244,109 fracture cases were included in this meta-analysis. Pooled analysis showed that PPI use could moderately increase the risk of hip fracture [RR = 1.26, 95 % confidence intervals (CIs) 1.16–1.36]. There was statistically significant heterogeneity among studies (p < 0.001; I 2 = 71.9 %). After limiting to cohort studies, there was also a moderate increase in hip fracture risk without evidence of study heterogeneity. Pooling revealed that short-term use ( 1 year) were similarly associated with increased risk of hip fracture. Furthermore, a moderately increased risk of spine (RR = 1.58, 95 % CI 1.38–1.82) and any-site fracture (RR = 1.33, 95 % CI 1.15–1.54) was also found among PPI users. In this update meta-analysis of observational studies, PPI use modestly increased the risk of hip, spine, and any-site fracture, but no evidence of duration effect in subgroup analysis.

Diabetes mellitus and risk of hip fractures: a meta-analysis

Abstract: This meta-analysis revealed that diabetic adults had a twofold greater risk of hip fractures compared with non-diabetic populations, and this association was more pronounced in type 1 diabetes. The relationship between diabetes mellitus and risk of hip fracture yielded conflicting results. We conducted a meta-analysis to investigate the association between diabetes mellitus and the risk of hip fractures based on observational studies. We conducted a systematic literature search of PubMed and Embase databases through May 2015. We selected cohort and case–control studies providing at least age-adjusted risk ratio (RR) and corresponding 95 % confidence intervals (CI) of hip fractures among diabetic and non-diabetic subjects. Moreover, we pooled the female-to-male RR of hip fractures from studies that reported gender-specific risk estimate in a single study. Twenty-one studies involving 82,293 hip fracture events among 6,995,272 participants were identified. Diabetes mellitus was associated with an increased risk of hip fractures (RR 2.07; 95 % CI 1.83–2.33) in a random effects model. Subgroup analysis indicated that excess risk of hip fracture was more pronounced in type 1 diabetes (RR 5.76; 95 % CI 3.66–9.07) than that in type 2 diabetes (RR 1.34; 95 % CI 1.19–1.51). The pooled female-to-male RR of hip fractures was 1.09 (95 % CI 0.93–1.28). Individuals with diabetes mellitus have an excessive risk of hip fractures, and this relationship is more pronounced in type 1 diabetes. The association between diabetes and hip fracture risk is similar in men and women.

Evidence of effectiveness of a fracture liaison service to reduce the re-fracture rate.

Abstract: We assessed the ability of a fracture liaison service (FLS) to directly reduce re-fracture risk. Having a FLS is associated with a ∼40 % reduction in the 3-year risk of major bone and ∼30 % of any bone re-fracture. The number needed to treat to prevent a re-fracture is 20. FLS have been promoted as the most effective interventions for secondary fracture prevention, and while there is evidence of increased rate of investigation and treatment at institutions with a FLS, only a few studies have considered fracture outcomes directly. We therefore sought to evaluate the ability of our FLS to reduce re-fracture risk. Historical cohort study of all patients ≥50 years presenting over a 6-month period with a minimal trauma fracture (MTF) to the emergency departments of a tertiary hospital with a FLS, and one without a FLS. Baseline characteristics, mortality and MTFs over a 3-year follow-up were recorded. Five hundred fifteen patients at the FLS hospital and 416 patients at the non-FLS hospital were studied. Over 3 years, 63/515 (12 %) patients at the FLS hospital and 70/416 (17 %) at the non-FLS hospital had a MTF. All patients were analysed in an intention-to-treat analysis regardless of whether they were seen in the FLS follow-up clinic. Statistical analysis using Cox proportional hazard models in the presence of a competing risk of death from any cause was used. After adjustment for baseline characteristics, there was a ∼30 % reduction in rate of any re-fracture at the FLS hospital (hazard ratio (HR) 0.67, confidence interval (CI) 0.47-0.95, p value 0.025) and a ∼40 % reduction in major re-fractures (hip, spine, femur, pelvis or humerus) (HR 0.59, CI 0.39-0.90, p value 0.013). We found a ∼30 % reduction in any re-fractures and a ∼40 % reduction in major re-fractures at the FLS hospital compared with a similar non-FLS hospital. The number of patients needed to treat to prevent one new fracture over 3 years is 20.

Relationship of sarcopenia and body composition with osteoporosis

Abstract: The purpose of the study is to investigate the relationship between sarcopenia and body composition and osteoporosis in cohorts of three different races with a total of 17,891 subjects. Lean mass and grip strength were positively associated with bone mineral densities (BMDs). Subjects with sarcopenia were two times more likely to have osteoporosis compared with normal subjects. The relationship between sarcopenia and osteoporosis is not totally clear. First, the present study assessed this relationship by using two different definitions for sarcopenia. Second, we examined the associations of body composition (including muscle mass as a major and important component) and muscle strength on regional and whole-body BMDs. In total, 17,891 subjects of African American, Caucasian, and Chinese ethnicities were analyzed. Sarcopenia was defined by relative appendicular skeletal muscle mass (RASM) cut points and also by the definition of the European Working Group on Sarcopenia in Older People (low RASM plus low muscle function). Multiple regression analyses were conducted to examine the association of fat mass, lean mass (including muscle mass), and grip strength with regional and whole-body BMDs. Multivariate logistic regression analysis was performed to explore the association between sarcopenia and osteopenia/osteoporosis. BMDs were positively associated with lean mass and negatively associated with fat mass, after controlling for potential confounders. Grip strength was significantly associated with higher BMDs. Each standard deviation (SD) increase in RASM resulted in a ~37 % reduction in risk of osteopenia/osteoporosis (odds ratio (OR) = 0.63; 95 % confidence interval (CI) = 0.59, 0.66). Subjects with sarcopenia defined by RASM were two times more likely to have osteopenia/osteoporosis compared with the normal subjects (OR = 2.04; 95 % CI = 1.61, 2.60). Similarly, subjects with sarcopenia (low muscle mass and low grip strength) were ~1.8 times more likely to have osteopenia/osteoporosis than normal subjects (OR = 1.87; 95 % CI = 1.09, 3.20). High lean mass and muscle strength were positively associated with BMDs. Sarcopenia is associated with low BMD and osteoporosis.

Hip fracture, mortality risk, and cause of death over two decades

Abstract: Men and women with hip fracture have higher short-term mortality. This study investigated mortality risk over two decades post-fracture; excess mortality remained high in women up to 10 years and in men up to 20 years. Cardiovascular disease (CVD) and pneumonia were leading causes of death with a long-term doubling of risk. Hip fractures are associated with increased mortality, particularly short term. In this study with a two-decade follow-up, we examined mortality and cause of death compared to the background population. We followed 1013 hip fracture patients and 2026 matched community controls for 22 years. Mortality, excess mortality, and cause of death were analyzed and stratified for age and sex. Hazard ratio (HR) was estimated by Cox regression. A competing risk model was fitted to estimate HR for common causes of death (CVD, cancer, pneumonia) in the short and long term (>1 year). For both sexes and at all ages, mortality was higher in hip fracture patients across the observation period with men losing most life years (p 80 years, for 5 years) and in men <80 years throughout. CVD and pneumonia were predominant causes of death in men and women with an associated higher risk in all age groups. Pneumonia caused excess mortality in men over the entire observation period. In a remaining lifetime perspective, all-cause and excess mortality after hip fracture was higher even over two decades of follow-up. CVD and pneumonia reduce life expectancy for the remaining lifetime and highlights the need to further improve post-fracture management.

Opportunistic screening for osteoporosis using the sagittal reconstruction from routine abdominal CT for combined assessment of vertebral fractures and density

Abstract: Opportunistic osteoporosis screening using abdominal CT scans obtained for other purposes has the potential to increase detection of those at increased risk for fragility fractures. We sought to combine the tasks of density measurement and vertebral fracture assessment on the sagittal view. We confirm that this represents a robust approach and recommend its implementation in clinical practice. Opportunistic osteoporosis screening at routine abdominal CT has been proposed by measuring axial (transverse) L1 trabecular attenuation and by sagittal reconstruction for vertebral fracture assessment. We sought to combine this dual evaluation on the sagittal reconstruction alone to improve efficiency. Routine contrast-enhanced abdominal CT scans performed for any indication on 571 consecutive adults age 60 years or older (mean age 70.7 years) were retrospectively analyzed. These were performed at a single center over a 3-month period. L1 trabecular attenuation was measured using an ovoid region-of-interest on both the transverse and sagittal series. The sagittal reconstruction was also analyzed for moderate-to-severe vertebral compression fractures using the Genant visual semi-quantitative method. Likely osteoporosis was defined by a moderate-to-severe fracture and/or sagittal L1 trabecular attenuation of ≤110 Hounsfield units (HU) (previously found to be >90 % specific for osteoporosis on our calibrated GE CT scanners at 120 kVp). Correlation was made with hip and spine dual X-ray absorptiometry (DXA). Mean absolute difference in L1 trabecular attenuation between transverse and sagittal reconstructions was 6.7 HU (±5.7) or 6.2 %. The transverse and sagittal HU measurements were in agreement (i.e., both measurements above or below this threshold) in 94.5 % of cases at the 110-HU cutoff. A total of 243 (42.3 %) patients had likely osteoporosis by CT criteria, of which only 48 (19.8 %) had previous DXA screening. Assessment of the sagittal view alone at routine abdominal CT for both vertebral fractures and trabecular bone mineral density provides a rapid and effective opportunistic screen for detecting individuals at increased risk for fragility fractures.

Osteogenesis imperfecta in children and adolescents—new developments in diagnosis and treatment

Abstract: Osteogenesis imperfecta (OI) is the most prevalent heritable bone fragility disorder in children. It has been known for three decades that the majority of individuals with OI have mutations in COL1A1 or COL1A2, the two genes coding for collagen type I alpha chains, but in the past 10 years defects in at least 17 other genes have been linked to OI. Almost all individuals with a typical OI phenotype have a mutation in one of the currently known genes. Regarding medical treatment, intravenous bisphosphonate therapy is the most widely used medical approach. This has a marked effect on vertebra in growing children and can lead to vertebral reshaping after compression fractures, but there is little effect of bisphosphonate therapy on the development of scoliosis. Bisphosphonate treatment decreases long-bone fracture rates, but such fractures are still frequent. Newer medications with anti-resorptive and bone anabolic action are being investigated in an attempt to improve on the efficacy of bisphosphonates but the safety and efficacy of these new approaches in children with OI is not yet established.

Rebound-associated vertebral fractures after discontinuation of denosumab—from clinic and biomechanics

Abstract: Summary Rebound-associated vertebral fractures may follow treatment discontinuation of highly potent reversible bone antiresorptives, resulting from the synergy of rapid bone resorption and accelerated microdamage accumulation in trabecular bone.

Teriparatide for osteoporosis: importance of the full course.

Abstract: Teriparatide (TPTD) is the only currently available therapeutic agent that increases the formation of new bone tissue and can provide some remediation of the architectural defects in the osteoporotic skeleton. The use of teriparatide clinically is limited to 24 months. We review clinical findings during daily teriparatide treatment over time. Teriparatide appears to increase bone formation more than bone resorption as determined biochemically and histologically. Teriparatide exerts its positive effects on bone formation in two distinct fashions. The first is direct stimulation of bone formation that occurs within active remodeling sites (remodeling-based bone formation) and on surfaces of bone previously inactive (modeling-based bone formation). The second is an increase in the initiation of new remodeling sites. Both processes contribute to the final increase in bone density observed by non-invasive tools such as DXA. Remodeling is the repair process by which skeletal tissue is maintained in a young healthy state, and when stimulated by TPTD is associated with a positive bone balance within each remodeling cavity. It seems likely therefore that this component will contribute to the anti-fracture efficacy of TPTD. Teriparatide reduces the risk of fracture, and this effect appears to increase with longer duration of therapy. The use of novel treatment regimens, including shorter courses, should be held in abeyance until controlled clinical trials are completed to define the relative fracture benefits of such approaches in comparison to the 24-month daily use of the agent.

Severe spontaneous vertebral fractures after denosumab discontinuation: three case reports.

Abstract: Osteoporosis treatments are usually given for a limited period of time in order to balance benefits and risks. We report three cases of postmenopausal women without any previous fragility fracture who presented severe spontaneous vertebral fractures after denosumab discontinuation. We think that the occurrence of these fractures could be explained by the severe rebound effect observed after denosumab discontinuation and that a consensus regarding the end of treatment with denosumab has to be defined.

Response of bone turnover markers to three oral bisphosphonate therapies in postmenopausal osteoporosis: the TRIO study

Abstract: Summary We used bone turnover markers to identify women who responded to bisphosphonate treatment for osteoporosis. Response was more likely with alendronate and ibandronate than risedronate. There was a greater decrease in bone markers if baseline bone turnover markers were higher and if the patient took more than 80 % of her medication.

Hip fracture incidence in Japan: Estimates of new patients in 2012 and 25-year trends.

Abstract: We estimated the number of hip fracture patients in 2012 in Japan and investigated the trends in incidence during a 25-year period from 1987 to 2012. Despite the increasing number of patients, the incidence of hip fracture in both men and women aged 70–79 years showed the possibility of decline. The objectives of this study were to estimate the number of hip fracture patients in 2012, to investigate the trends in incidence during a 25-year period from 1987 to 2012, and to determine the regional differences in Japan. Data were collected through a nationwide survey based on hospitals by a mail-in survey. Hip fracture incidences by sex and age and standardized incidence ratios by region were calculated. The estimated numbers of new hip fracture patients in 2012 were 175,700 in total (95 % CI 170,300–181,100), 37,600 (36,600–38,600) for men and 138,100 (134,300–141,900) for women. The incidence rates in both men and women aged 70–79 years were the lowest in the 20-year period from 1992 to 2012. The incidence was higher in western areas of Japan than that in eastern areas in both men and women; however, the difference in the incidence of hip fracture between western and eastern areas is becoming smaller. Despite the increasing number of new patients, the incidence of hip fracture in both men and women aged 70–79 years showed the possibility of decline. The exact reasons for this are unknown, but various drugs for improving bone mineral density or preventing hip fracture might have influenced the results. A decrease in the differences in nutrient intake levels might explain some of the change in regional differences in Japan.

The management of osteoporosis in children

Abstract: This article reviews the manifestations and risk factors associated with osteoporosis in childhood, the definition of osteoporosis and recommendations for monitoring and prevention. As well, this article discusses when a child should be considered a candidate for osteoporosis therapy, which agents should be prescribed, duration of therapy and side effects. There has been significant progress in our understanding of risk factors and the natural history of osteoporosis in children over the past number of years. This knowledge has fostered the development of logical approaches to the diagnosis, monitoring, and optimal timing of osteoporosis intervention in this setting. Current management strategies are predicated upon monitoring at-risk children to identify and then treat earlier rather than later signs of osteoporosis in those with limited potential for spontaneous recovery. On the other hand, trials addressing the prevention of the first-ever fracture are still needed for children who have both a high likelihood of developing fractures and less potential for recovery. This review focuses on the evidence that shapes the current approach to diagnosis, monitoring, and treatment of osteoporosis in childhood, with emphasis on the key pediatric-specific biological principles that are pivotal to the overall approach and on the main questions with which clinicians struggle on a daily basis. The scope of this article is to review the manifestations of and risk factors for primary and secondary osteoporosis in children, to discuss the definition of pediatric osteoporosis, and to summarize recommendations for monitoring and prevention of bone fragility. As well, this article reviews when a child is a candidate for osteoporosis therapy, which agents and doses should be prescribed, the duration of therapy, how the response to therapy is adjudicated, and the short- and long-term side effects. With this information, the bone health clinician will be poised to diagnose osteoporosis in children and to identify when children need osteoporosis therapy and the clinical outcomes that gauge efficacy and safety of treatment.

DNA sequence analysis in 598 individuals with a clinical diagnosis of osteogenesis imperfecta: diagnostic yield and mutation spectrum.

Abstract: We detected disease-causing mutations in 585 of 598 individuals (98 %) with typical features of osteogenesis imperfecta (OI). In mild OI, only collagen type I encoding genes were involved. In moderate to severe OI, mutations in 12 different genes were found; 11 % of these patients had mutations in recessive genes. OI is usually caused by mutations in COL1A1 or COL1A2, the genes encoding collagen type I alpha chains, but mutations in at least 16 other genes have also been associated with OI. It is presently unknown what proportion of individuals with clinical features of OI has a disease-causing mutation in one of these genes. DNA sequence analysis was performed on 598 individuals from 487 families who had a typical OI phenotype. OI type I was diagnosed in 43 % of individuals, and 57 % had moderate to severe OI, defined as OI types other than type I. Disease-causing variants were detected in 97 % of individuals with OI type I and in 99 % of patients with moderate to severe OI. All mutations found in OI type I were dominant and exclusively affected COL1A1 or COL1A2. In moderate to severe OI, dominant mutations were found in COL1A1/COL1A2 (77 %), IFITM5 (9 %), and P4HB (0.6 %). Mutations in one of the recessive OI-associated gene were observed in 12 % of individuals with moderate to severe OI. The genes most frequently involved in recessive OI were SERPINF1 (4.0 % of individuals with moderate to severe OI) and CRTAP (2.9 %). DNA sequence analysis of currently known OI-associated genes identifies disease-causing variants in almost all individuals with a typical OI phenotype. About 20 % of individuals with moderate to severe OI had mutations in genes other than COL1A1/COL1A2.

Effect of osteoporosis medications on fracture healing

Abstract: Antiosteoporotic medications are often used to concurrently treat a patient's fragility fractures and underlying osteoporosis. This review evaluates the existing literature from animal and clinical models to determine these drugs' effects on fracture healing. The data suggest that these medications may enhance bone healing, yet more thorough prospective studies are warranted. Pharmacologic agents that influence bone remodeling are an essential component of osteoporosis management. Because many patients are first diagnosed with osteoporosis when presenting with a fragility fracture, it is critical to understand how osteoporotic medications influence fracture healing. Vitamin D and its analogs are essential for the mineralization of the callus and may also play a role in callus formation and remodeling that enhances biomechanical strength. In animal models, antiresorptive medications, including bisphosphonates, denosumab, calcitonin, estrogen, and raloxifene, do not impede endochondral fracture healing but may delay repair due to impaired remodeling. Although bisphosphonates and denosumab delay callus remodeling, they increase callus volume and result in unaltered biomechanical properties. Calcitonin increases cartilage formation and callus maturation, resulting in improved biomechanical properties. Parathyroid hormone, an anabolic agent, has demonstrated promise in animal models, resulting in accelerated healing with increased callus volume and density, more rapid remodeling to mature bone, and improved biomechanical properties. Clinical data with parathyroid hormone have demonstrated enhanced healing in distal radius and pelvic fractures as well as postoperatively following spine surgery. Strontium ranelate, which may have both antiresorptive and anabolic properties, affects fracture healing differently in normal and osteoporotic bone. While there is no effect in normal bone, in osteoporotic bone, strontium ranelate increases callus bone formation, maturity, and mineralization; forms greater and denser trabeculae; and improves biomechanical properties. Further clinical studies with these medications are needed to fully understand their effects on fracture healing in order to simultaneously treat fragility fractures and underlying osteoporosis.

The current economic burden of illness of osteoporosis in Canada

Abstract: We estimate the current burden of illness of osteoporosis in Canada is double ($4.6 billion) our previous estimates ($2.3 billion) due to improved data capture of the multiple encounters and services that accompany a fracture: emergency room, admissions to acute and step-down non-acute institutions, rehabilitation, home-assisted or long-term residency support. We previously estimated the economic burden of illness of osteoporosis-attributable fractures in Canada for the year 2008 to be $2.3 billion in the base case and as much as $3.9 billion. The aim of this study is to update the estimate of the economic burden of illness for osteoporosis-attributable fractures for Canada based on newly available home care and long-term care (LTC) data. Multiple national databases were used for the fiscal-year ending March 31, 2011 (FY 2010/2011) for acute institutional care, emergency visits, day surgery, secondary admissions for rehabilitation, and complex continuing care, as well as national dispensing data for osteoporosis medications. Gaps in national data were supplemented by provincial and community survey data. Osteoporosis-attributable fractures for Canadians age 50+ were identified by ICD-10-CA codes. Costs were expressed in 2014 dollars. In FY 2010/2011, the number of osteoporosis-attributable fractures was 131,443 resulting in 64,884 acute care admissions and 983,074 acute hospital days. Acute care costs were $1.5 billion, an 18 % increase since 2008. The cost of LTC was 33.4 times the previous estimate ($31 million versus $1.03 billion) because of improved data capture. The cost for rehabilitation and secondary admissions increased 3.4 fold, while drug costs decreased 19 %. The overall cost of osteoporosis was over $4.6 billion, an increase of 83 % from the 2008 estimate. Since the 2008 estimate, new Canadian data on home care and LTC are available which provided a better estimate of the burden of osteoporosis in Canada. This suggests that our previous estimates were seriously underestimated.

Sclerostin-antibody treatment of glucocorticoid-induced osteoporosis maintained bone mass and strength

Abstract: Summary This study was to determine if antibody against sclerostin (Scl-Ab) could prevent glucocorticoid (GC)-induced osteoporosis in mice We found that Scl-Ab prevented GC-induced reduction in bone mass and bone strength and that the anabolic effects of Scl-Ab might be partially achieved through the preservation of osteoblast activity through autophagy

Fracture risk in oral glucocorticoid users: a Bayesian meta-regression leveraging control arms of osteoporosis clinical trials

Abstract: Little data exist on the frequency of fracture among oral glucocorticoid users. We examined the effect of oral glucocorticoids on fracture incidence using data from randomized controlled trials. Patients starting glucocorticoids had a higher probability of fracture and decline in bone mineral density compared to chronic glucocorticoid users. Oral glucocorticoids (GCs) are the leading cause of secondary osteoporosis. However, there have been few studies that quantify the rate of fracture among GC users. We sought to provide a pooled estimate of fracture risk from randomized controlled trials (RCTs) of GC-treated patients. We updated a MEDLINE search published by the American College of Rheumatology through to March 2015 and identified RCTs of osteoporosis therapies that reported fracture and bone mineral density (BMD) among oral GC users. We restricted the analysis to placebo or control arms. RCT arms were stratified by GC exposure at enrolment to GC initiators (≤6 months) and chronic GC users (>6 months). Bayesian meta-regression was used to estimate the annual probability of vertebral fracture (primary), non-vertebral fracture and percentage change in lumbar spine and femoral neck BMD. The annual incidence of vertebral and non-vertebral fracture was 5.1 % (95 % CrI = 2.8–8.2) and 2.5 % (95 % CrI = 1.2–-4.2) among GC initiators, and 3.2 % (95 % CrI = 1.8–5.0) and 3.0 % (95 % CrI = 0.8–5.9) among chronic GC users. Our meta-regression identified a non-significant effect of group-level variables (mean age, mean BMD, mean GC daily dose, patients with previous vertebral fractures, proportion of women and adjuvant used) on vertebral fracture rate. Our study found higher vertebral fracture incidence among GC initiators, yet a relative decline in fracture incidence with longer exposure. Our findings suggest that fracture incidence among oral GC users may be more common than previously estimated. Optimizing GC-induced osteoporosis management during early exposure to GC is essential to prevent fractures.

Osteonecrosis of the jaw (ONJ): diagnosis and management in 2015

Abstract: Osteonecrosis of the jaw (ONJ) has been associated with the use of aminobisphosphonates and denosumab. The vast majority (>90%) of cases occur in the oncology patient population receiving high doses of intravenous bisphosphonates or subcutaneous denosumab. The incidence of ONJ in the osteoporosis patient population is very low and is estimated at 1-90 per 100,000 patient-years of exposure. In the oncology patient population the incidence appears to be related to dose and duration of exposure, and prevalence has been estimated to be as high as 18.6%. A number of risk factors in addition to antiresorptive therapy have been identified. These include the presence of periodontal disease, oral surgical procedures with extractions or implants, radiation therapy, chemotherapy, diabetes, glucocorticoid use, and smoking. Antiangiogenic agents appear to contribute to the risk of ONJ, however, data at this time are limited and further evidence is required prior to confirming a causal relationship. ONJ may be prevented with optimization of oral hygiene, the use of oral antimicrobial mouth rinses, as well as systemic antibiotic therapy. Individuals not responding to conservative management or in the advanced stages of ONJ may be considered for surgery, as data over the past several years have demonstrated surgical success in this patient population. Case reports have indicated that teriparatide may enhance healing. A number of experimental therapies are being evaluated and include the use of bone marrow stem cell intralesional transplantation, local application of platelet-derived growth factor, hyperbaric oxygen, tissue grafting, and low-level laser therapy. This paper summarizes the current research as well as the international consensus on the diagnosis and management of ONJ.

Patient-specific finite element estimated femur strength as a predictor of the risk of hip fracture: the effect of methodological determinants.

Abstract: Summary A finite element modelling pipeline was adopted to predict femur strength in a retrospective cohort of 100 women. The effects of the imaging protocol and the meshing technique on the ability of the femur strength to classify the fracture and the control groups were analysed.

Teriparatide improves volumetric bone mineral density and fine bone structure in the UIV+1 vertebra, and reduces bone failure type PJK after surgery for adult spinal deformity

Abstract: We conducted a prospective comparative study of the effect of teriparatide therapy for preventing vertebral-failure-type PJK after reconstructive surgery for adult spinal deformity. Prophylactic teriparatide improved the volumetric bone mineral density and fine bone structure of the vertebra above the upper-instrumented vertebra and reduced the incidence of vertebral-failure-type PJK. Proximal junctional kyphosis (PJK) is a complication after corrective surgery for spinal deformity. This study sought to determine whether teriparatide (TP) is an effective prophylactic against PJK type 2 (vertebral fracture) in surgically treated patients with adult spinal deformity (ASD). Forty-three patients who started TP therapy immediately after surgery and 33 patients who did not receive TP were enrolled in this prospective case series. These patients were female, over 50, surgically treated for ASD, and followed for at least 2 years. Preoperative and postoperative standing whole-spine X-rays and dual-energy X-ray absorptiometry scans, and multidetector CT images obtained before and 6 months after surgery were used to analyze the bone strength in the vertebra above the upper-instrumented vertebra (UIV+1). Mean age was 67.9 years. After 6 months of treatment, mean hip-bone mineral density (BMD) increased from 0.721 to 0.771 g/cm2 in the TP group and decreased from 0.759 to 0.729 g/cm2 in the control group. This percent BMD change between groups was significant (p < 0.05). The volumetric BMD (326 to 366 mg/cm3) and bone mineral content (BMC) (553 to 622 mg) at UIV+1 were also significantly increased in TP group. The bone volume/tissue volume ratio increased from 46 to 54 % in the TP group, and the trabecular bone thickness and number increased by 14 and 5 %, respectively. At the 2-year follow-up, the PJK type 2 incidence was significantly lower in the TP group (4.6 %) than in the control group (15.2 %; p = .02). Prophylactic TP treatment improved the volumetric BMD and fine bone structure at UIV+1 and reduced the PJK-type 2 incidence.

Current trends and future projections of hip fracture in South Korea using nationwide claims data.

Abstract: Incidence of hip fracture increased in Korean populations over age 50 between 2008 and 2012, and the number of fractures was predicted to increase by 1.4 times by 2025. This is important information for public health planning. The purposes of this study were to evaluate the trends in the incidence and mortality of hip fracture between 2008 and 2012 and predict the number of hip fractures in Korea through 2025 using nationwide claims data. The data managed by the National Health Insurance Service were used to identify the hip fractures in patients aged >50 years between 2008 and 2012. Projections of hip fractures were conducted using the Poisson distribution from 2016 to 2025 in Korea. The incidence of hip fractures (per 100,000) increased by 14.1 % over the 5 years of the study, by 15.8 % in women and 10.9 % in men; the older age group showed a steep rise and shift in the incidence from 2008 to 2012. The cumulative mortality rates at 1 year after hip fractures were 17.2 % (3575/20,849) in 2008 and 16.0 % (4547/28,426) in 2012. Overall standardized mortality ratios (SMRs) for hip fracture were higher in men (11.93) than in women (11.22) and were higher than those in the general population in all age groups. In 2016, the total number of hip fractures was estimated to increase an overall of 1.4 times by 2025. The incidence of hip fracture continues to increase, and the related mortality is still high, although it has decreased over time. The socioeconomic burden of hip fracture is expected to increase in Korea along with the increased estimated number of fractures. Nationwide strategies should include attempts to reduce the future socioeconomic burdens of hip fractures.

Rapamycin reduces severity of senile osteoporosis by activating osteocyte autophagy

Abstract: Osteocyte is the orchestrator of bone remolding and decline in osteocyte autophagy is involved in senile osteoporosis. Our results suggested that rapamycin, at least in part by activating osteocyte autophagy, reduced the severity of age-related bone changes in trabecular bone of old male rats. Previous literatures have showed that osteocyte is the orchestrator of bone remolding and age-related decline in osteocyte number is associated with senile osteoporosis. Autophagy is an important cellular protective mechanism which can preserve osteocyte viability and failure of autophagy in osteocyte with age has been linked to senile osteoporosis. The purpose of this study was to explore whether rapamycin, one activator of autophagy, has protective effects on senile osteoporosis through inducing osteocyte autophagy. Fifty-two 24-month-old male Sprague-Dawley (SD) rats were randomly divided into two groups. Rapamycin (1 mg/kg weight/day) or DMSO vehicle control was administered intraperitoneally for 12 weeks. BMD and bone microstructure were determined by Micro-CT. Fluorochrome labeling of the bones was performed to measure the mineral apposition rate (MAR). TRAP staining was performed to evaluate osteoclast number. The plasma levels of bone turnover markers were also analyzed. The effects of rapamycin on osteocyte autophagy were determined by immunohistochemistry, Western blot, and q-PCR. TUNEL was used to determine the prevalence of osteocyte apoptosis. Micro-CT evaluation demonstrated that rapamycin had a protective effect on age-related bone loss in trabecular bone. Besides, rapamycin resulted in an obvious increase of MAR and a decrease of osteoclast number in contrast to the control group. Furthermore, rapamycin also induced autophagy in osteocyte demonstrated by increased LC3-positive osteocyte and increased LC3 turnover. In addition, rats treated with rapamycin exhibited decreased apoptosis of osteocyte determined by TUNEL. These results suggested that rapamycin, at least in part by activating osteocyte autophagy, reduced the severity of age-related bone changes in trabecular bone of old male rats. Therefore, rapamycin might be a feasible therapeutic approach for senile osteoporosis.

Alkaline biodegradable implants for osteoporotic bone defects—importance of microenvironment pH

Abstract: Change of microenvironment pH by biodegradable implants may ameliorate unbalanced osteoporotic bone remodeling. The present work demonstrated that a weak alkaline condition stimulated osteoblasts differentiation while suppressed osteoclast generation. In vivo, implants with an alkaline microenvironment pH (monitored by a pH microelectrode) exhibited a promising healing effect for the repair of osteoporotic bone defects. Under osteoporotic conditions, the response of the bone microenvironment to an endosseous implant is significantly impaired, and this substantially increases the risk of fracture, non-union and aseptic implant loosening. Acid-base equilibrium is an important factor influencing bone cell behaviour. The present purpose was to study the effect of a series of alkaline biodegradable implant materials on regeneration of osteoporotic bone defect, monitoring the microenvironment pH (μe-pH) over time. The proliferation and differentiation potential of osteoporotic rat bone marrow stromal cells and RAW 264.7 cells were examined under various pH conditions. Ovariectomized rat bone defects were filled with specific biodegradable materials, and μe-pH was measured by pH microelectrode. New osteoid and tartrate-resistant acid phosphatase-positive osteoclast-like cells were examined by Goldner’s trichrome and TRAP staining, respectively. The intermediate layer between implants and new bone were studied using energy-dispersive X-ray spectroscopy (EDX) linear scanning. In vitro, weak alkaline conditions stimulated osteoporotic rat bone marrow stromal cells (oBMSC) differentiation, while inhibiting the formation of osteoclasts. In vivo, μe-pH differs from that of the homogeneous peripheral blood and exhibits variations over time particular to each material. Higher initial μe-pH was associated with more new bone formation, late response of TRAP-positive osteoclast-like cells and the development of an intermediate ‘apatitic’ layer in vivo. EDX suggested that residual material may influence μe-pH even 9 weeks post-surgery. The pH microelectrode is suitable for in vivo μe-pH detection. Alkaline biodegradable materials generate an in vivo microenvironmental pH which is higher than the normal physiological value and show promising healing effects in the context of osteoporotic bone defects.

Effect of IV contrast on lumbar trabecular attenuation at routine abdominal CT: correlation with DXA and implications for opportunistic osteoporosis screening

Abstract: Osteoporosis remains under-diagnosed. Routine abdominal CT can provide opportunistic screening, but the effect of IV contrast is largely unknown. The overall performance for predicting osteoporosis was similar between enhanced and unenhanced scans. Therefore, both non-contrast and contrast-enhanced abdominal CT scans can be employed for opportunistic osteoporosis screening. Osteoporosis is an important yet under-diagnosed public health concern. Lumbar attenuation measurement at routine abdominal CT can provide a simple opportunistic initial screen, but the effect of IV contrast has not been fully evaluated. Mean trabecular CT attenuation values (in Hounsfield units, HU) at the L1 vertebral level were measured by oval region-of-interest (ROI) on both the unenhanced and IV-contrast-enhanced CT series in 157 adults (mean age, 62.0). All patients underwent correlative central DXA within 6 months of CT. Based on DXA BMD of the lumbar spine, femoral neck, and total proximal femur: osteoporosis, osteopenia, and normal BMD was present in 33, 77, and 47, respectively. Statistical analysis included Bland-Altman plots and receiver operating characteristic (ROC) curves. Mean difference (±SD) in L1 trabecular attenuation between enhanced and unenhanced CT series was +11.2 HU (±19.2) (95 % CI, 8.16–14.22 HU), an 8 % difference. Intra-patient variation was substantial, but no overall trend in the HU difference was seen according to underlying BMD. ROC area under the curve (AUC) for unenhanced and enhanced CT for diagnosing osteoporosis were similar at 0.818 and 0.830, respectively (p = 0.632). Thresholds for maintaining 90 % specificity for osteoporosis were 90 HU for unenhanced and 102 HU for enhanced CT. Thresholds for maintaining 90 % sensitivity for osteoporosis were 139 HU for unenhanced and 144 HU for enhanced CT. Similar diagnostic performance was seen for diagnosing low BMD (osteoporosis or osteopenia) using higher HU cut-offs. Contrast-enhanced CT shows an average increase of 11 HU over the unenhanced series for L1 trabecular attenuation. The overall performance for predicting osteoporosis is similar between the enhanced and unenhanced scans, thus either can be employed for initial opportunistic screening.