Differences in femoral fracture localizations in men and women in Switzerland between 1998 and 2021-reversal of the secular trend?

Number and age-standardized incidences of femoral fractures by sex and localization were determined annually between 1998 and 2021 in subjects aged 45 years or older living in Switzerland. The number and incidences of femoral neck, pertrochanteric, subtrochanteric, and femoral shaft fractures followed distinct unexpected trend patterns. INTRODUCTION: Long-term incidence trends for femoral fractures by individual localizations are unknown. METHODS: Annual absolute number of hospitalizations and median age at hospital admission between 1998 and 2021 were extracted from the medical database of the Swiss Federal Office of Statistics by sex and 10-year age groups for the following 10th International Classification of Diseases (ICD-10) codes: femoral neck (ICD-10 S72.0), pertrochanteric (S72.1), subtrochanteric (S72.2), and femoral shaft fractures (S72.3). Age-standardized incidence rates (ASI) and corresponding trends were calculated. RESULTS: Over 24 years, the number of femoral neck fractures increased in men (+ 45%) but decreased in women (- 7%) with ASI significantly decreasing by 20% and 37% (p < 0.001 for trend for both), respectively. By contrast, the number of pertrochanteric fractures increased by 67% and 45% in men and women, respectively, corresponding to a horizontal ASI-trend in men (n.s.) and a modest significant decreasing ASI-trend in women (p < 0.001). The number of subtrochanteric fractures increased in both sexes with corresponding modest significant reductions in ASI-trends (p = 0.015 and 0.002, respectively). Femoral shaft fractures almost doubled in men (+ 71%) and doubled in women (+ 100%) with corresponding significant increases in ASI-trends (p = 0.001 and p < 0.001, respectively). Age at admission increased for all fracture localizations, more so in men than in women and more so for subtrochanteric and shaft fractures than for "typical" hip fractures. CONCLUSION: Incidence changes of pertrochanteric fractures and femoral shaft fractures deserve increased attention, especially in men. Pooling diagnostic codes for defining hip fractures may hide differing patterns by localization and sex.

Hospitalizations for major osteoporotic fractures in Switzerland: a long-term trend analysis between 1998 and 2018.

Between 1998 and 2018, the number of hospitalizations for major osteoporotic fractures increased. After standardization for age, these numerical increases translated into a reduced incidence of hospitalizations for hip fractures and an increased incidence of hospitalizations for spine, proximal humerus, and distal radius fractures in both sexes. INTRODUCTION: The longterm epidemiological trends of hospitalizations for major osteoporotic fractures (MOF) between 1998 and 2018 in Switzerland are unknown. METHODS: The absolute number of acute hospitalizations for MOF (hip fractures and fractures of the spine, proximal humerus, and distal radius) and related length of acute hospital stay were extracted from the medical database of the Swiss Federal Office of Statistics. Age-standardized incidence rates were calculated using 1998 as the reference year. RESULTS: Hospitalizations for MOF increased from 4483 to 7542 (+ 68.2%) in men and from 13,242 to 19,362 (+ 46.2%) in women. The age-standardized incidence of hospitalizations for MOF increased by 5.7% in men (p = 0.002) and by 5.1% in women (p = 0.018). The age-standardized incidence of hip fractures decreased by 15.3% in men (p < 0.001) and by 21.5% in women (p < 0.001). In parallel, the age-standardized incidence of MOF other than hip fractures increased by 31.8% in men (p < 0.001) and by 40.1% in women (p < 0.001). The mean length of acute hospital stays for MOF decreased from 16.3 to 8.5 days in men and from 16.9 to 8.1 days in women. CONCLUSION: Between 1998 and 2018, the number of hospitalizations for MOF increased significantly by a larger extent than expected based on the ageing of the Swiss population alone. This increase was solely driven by an increased incidence of MOF other than hip fractures as incident hip fractures decreased over time in both sexes, more so in women than in men.

Induced Experimental Peri-Implantitis and Periodontitis: What Are the Differences in the Inflammatory Response?

This preliminary study investigates the differences between experimental periodontitis and peri-implantitis in a dog model, with a focus on the histopathology, inflammatory responses, and specific immunoregulatory activities driven by Th1/Th2-positive cells. Twelve dental implants were inserted into the edentulated posterior mandibles of 6 beagle dogs and were given 12 weeks for osseointegration. Experimental peri-implantitis and periodontitis (first mandible molar) were then induced using cotton-floss ligatures. Twelve weeks later, alveolar bones were quantitated by cone beam-computer tomography. Histopathologic analysis of the inflamed gingiva and periodontal tissues was performed by light microscopy, and the Th1/Th2 cell populations were investigated by flow cytometry. Peri-implantitis and periodontitis were both found to be associated with pronounced bone resorption effects, both to a similar degree vertically, but with a differential bone resorption pattern mesio-distally, and with a significantly higher and consistent bone resorption result in peri-implantitis, although with a higher variance of bone resorption in periodontitis. The histologic appearances of the inflammatory tissues were identical. The percentages of Th1/Th2 cells in the inflamed gingival tissues of both experimental peri-implantitis and periodontitis were also found to be similar. Experimental periodontitis and peri-implantitis in the dog model show essentially the same cellular pathology of inflammation. However, bone resorption was found to be significantly higher in peri-implantitis; the histopathologic changes in the periodontal tissues were similar in both groups but showed a higher interindividual variation in periodontitis and appeared more uniform in peri-implantitis. This preliminary study indicates that more focused experimental in vivo inflammation models need to be developed to better simulate the human pathology in the 2 different diseases and to have a valuable tool to investigate more specifically how novel treatments/prevention approaches may heal the differential adverse effects on bone tissue and on periodontium in periodontitis and in periimplantitis.

A Bibliometric Analysis of Fragility Fractures: Top 50.

Background and Objectives: The population is aging and fragility fractures are a research topic of steadily growing importance. Therefore, a systematic bibliometric review was performed to identify the 50 most cited articles in the field of fragility fractures analyzing their qualities and characteristics. Materials and Methods: From the Core Collection database in the Thomson Reuters Web of Knowledge, the most influential original articles with reference to fragility fractures were identified in February 2021 using a multistep approach. Year of publication, total number of citations, average number of citations per year since year of publication, affiliation of first and senior author, geographic origin of study population, keywords, and level of evidence were of interest. Results: Articles were published in 26 different journals between 1997 and 2020. The number of total citations per article ranged from 12 to 129 citations. In the majority of publications, orthopedic surgeons and traumatologists (66%) accounted for the first authorship, articles mostly originated from Europe (58%) and the keyword mostly used was "hip fracture". In total, 38% of the articles were therapeutic studies level III followed by prognostic studies level I. Only two therapeutic studies with level I could be identified. Conclusions: This bibliometric review shows the growing interest in fragility fractures and raises awareness that more high quality and interdisciplinary studies are needed.

Osteoporosis in the lower extremities in chronic spinal cord injury.

STUDY DESIGN: Cross-sectional study. OBJECTIVES: To investigate the effect of chronic motor complete spinal cord injury (SCI) and sex on bone densitometry parameters of the hip, femoral neck, tibial epiphysis, and diaphysis and on long bone fractures. SETTING: SCI rehabilitation center. METHODS: Women and men with long-term (≥7 years) motor complete SCI were compared with able-bodied women and men. Dual-energy X-ray absorptiometry was used to assess bone densitometry parameters at the hip and femoral neck, whereas peripheral quantitative computed tomography was used for the tibial epiphysis and diaphysis. RESULTS: The data of 18 women and 25 men with SCI with a mean age of 54.7 ± 12.4 and 53.5 ± 8.6 years, respectively, were analyzed. As reference groups, 74 able-bodied women and 46 men with a mean age of 51.0 ± 13.1 and 50.9 ± 11.2 years were evaluated. Most bone densitometry values were significantly (p ≤ 0.033) lower in the SCI compared with the reference groups, including total bone mineral density at the distal tibial epiphysis (-58.0% in SCI women and -53.6% in SCI men). Fracture rates per 100 patient-years were 3.17 and 2.66 in women and men with SCI compared with 0.85 and 0.21 in able-bodied women and men, respectively. CONCLUSIONS: Compared with able-bodied women and men, individuals with chronic motor complete SCI showed considerably lower bone densitometry values and a higher historical fracture rate. These findings support the need for preventative and therapeutic strategies against bone loss in individuals with SCI.

Bone Mineral Density Changes After 1 Year of Denosumab Discontinuation in Postmenopausal Women with Long-Term Denosumab Treatment for Osteoporosis.

The aim of the present study was to document the changes in bone mineral density (BMD) 1 year after denosumab loss-of-effect following long-term treatment with subcutaneous denosumab 60 mg Q6M during 7 or 10 years and in the absence of any treatment with a bone active substance. All postmenopausal women with osteoporosis who participated to the randomized placebo-controlled FREEDOM core trial and its open-label extension at the University Hospital of Bern, Switzerland, and who accepted to undergo off-treatment follow-up during 1 year after discontinuation, were included (N = 12). After 10 years of denosumab, mean lumbar spine (LS) BMD had increased by 21.2% vs. baseline. One year after discontinuation LS BMD had decreased by - 9.1% vs. Year 10, resulting in a net gain of 10.2% vs. baseline. At total hip (TH) and femoral neck (FN), BMD had increased by 8.3 and 8.1% in Year 10 vs. baseline, respectively. 1 Year after discontinuation, BMD had decreased by - 12.7 and - 11.0% vs. Year 10, respectively, corresponding to net BMD losses of - 5.5 and - 3.8% vs. baseline, respectively. Similar albeit less pronounced changes were observed in those treated with denosumab during 7 years. Stopping denosumab after long-term exposure resulted in BMD losses of large order of magnitude at all measured sites, suggesting that treatment duration may predict the rate and amount of bone lost.

Reduction of falls and fractures after permanent pacemaker implantation in elderly patients with sinus node dysfunction.

AIMS: Elderly patients with sinus node dysfunction (SND) are at increased risk of falls with possible injuries. However, the incidence of these adverse events and its reduction after permanent pacemaker (PPM) implantation are not known. METHODS AND RESULTS: Eighty-seven patients (mean [SD] age 75.4 [8.3] years, 51% women) with SND and an indication for cardiac pacing were included and were examined by a standardized interview targeting fall history. The incidence and total number of falls, falls with injury, falls requiring treatment, and falls resulting in a fracture were assessed for the time period of 12 months before (retrospectively) and after PPM implantation (prospectively). Furthermore, symptoms such as syncope, dizziness, and dyspnea were evaluated before and after PPM implantation. The implantation of a PPM was associated with a reduced proportion of patients experiencing at least one fall by 71% (from 53 to 15%, P < 0.001) and a reduction of the absolute number of falls by 90% (from 127 to 13, P < 0.001) during the 12 months before vs. after PPM implant. Falls with injury (28 vs. 10%, P = 0.005), falls requiring medical attention (31 vs. 8%, P < 0.001), and falls leading to fracture (8 vs. 0%, P = 0.013) were similarly reduced. Notably, fewer patients had syncope (4 vs. 45%, P < 0.001) and dizziness after PPM implantation (12 vs. 45%, P < 0.001). CONCLUSION: Falls, fall-related injuries, and fall-related fractures are frequent in SND patients. Permanent pacemaker implantation is associated with a significantly reduced risk of these adverse events, although no causal relationship could be established due to the study design.

Bone mineral density (BMD) and vertebral trabecular bone score (TBS) for the identification of elderly women at high risk for fracture: the SEMOF cohort study.

PURPOSE: To determine the predictive value of the vertebral trabecular bone score (TBS) alone or in addition to bone mineral density (BMD) with regard to fracture risk. METHODS: Retrospective analysis of the relative contribution of BMD [measured at the femoral neck (FN), total hip (TH), and lumbar spine (LS)] and TBS with regard to the risk of incident clinical fractures in a representative cohort of elderly post-menopausal women previously participating in the Swiss Evaluation of the Methods of Measurement of Osteoporotic Fracture Risk study. RESULTS: Complete datasets were available for 556 of 701 women (79 %). Mean age 76.1 years, LS BMD 0.863 g/cm2, and TBS 1.195. LS BMD and LS TBS were moderately correlated (r 2 = 0.25). After a mean of 2.7 ± 0.8 years of follow-up, the incidence of fragility fractures was 9.4 %. Age- and BMI-adjusted hazard ratios per standard deviation decrease (95 % confidence intervals) were 1.58 (1.16-2.16), 1.77 (1.31-2.39), and 1.59 (1.21-2.09) for LS, FN, and TH BMD, respectively, and 2.01 (1.54-2.63) for TBS. Whereas 58 and 60 % of fragility fractures occurred in women with BMD T score ≤-2.5 and a TBS <1.150, respectively, combining these two thresholds identified 77 % of all women with an osteoporotic fracture. CONCLUSIONS: Lumbar spine TBS alone or in combination with BMD predicted incident clinical fracture risk in a representative population-based sample of elderly post-menopausal women.

Fracture risk and zoledronic acid therapy in men with osteoporosis.

BACKGROUND: Fractures in men are a major health issue, and data on the antifracture efficacy of therapies for osteoporosis in men are limited. We studied the effect of zoledronic acid on fracture risk among men with osteoporosis. METHODS: In this multicenter, double-blind, placebo-controlled trial, we randomly assigned 1199 men with primary or hypogonadism-associated osteoporosis who were 50 to 85 years of age to receive an intravenous infusion of zoledronic acid (5 mg) or placebo at baseline and at 12 months. Participants received daily calcium and vitamin D supplementation. The primary end point was the proportion of participants with one or more new morphometric vertebral fractures over a period of 24 months. RESULTS: The rate of any new morphometric vertebral fracture was 1.6% in the zoledronic acid group and 4.9% in the placebo group over the 24-month period, representing a 67% risk reduction with zoledronic acid (relative risk, 0.33; 95% confidence interval, 0.16 to 0.70; P=0.002). As compared with men who received placebo, men who received zoledronic acid had fewer moderate-to-severe vertebral fractures (P=0.03) and less height loss (P=0.002). Fewer participants who received zoledronic acid had clinical vertebral or nonvertebral fractures, although this difference did not reach significance because of the small number of fractures. Bone mineral density was higher and bone-turnover markers were lower in the men who received zoledronic acid (P<0.05 for both comparisons). Results were similar in men with low serum levels of total testosterone. The zoledronic acid and placebo groups did not differ significantly with respect to the incidence of death (2.6% and 2.9%, respectively) or serious adverse events (25.3% and 25.2%). CONCLUSIONS: Zoledronic acid treatment was associated with a significantly reduced risk of vertebral fracture among men with osteoporosis. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT00439647.).

Primary male osteoporosis is associated with enhanced glucocorticoid availability.

OBJECTIVE: While systemic glucocorticoids compromise bone metabolism, altered intracellular cortisol availability may also contribute to the pathogenesis of primary male osteoporosis (MO). The objective of this study was to assess whether intracellular cortisol availability is increased in MO due to a distorted local cortisol metabolism. METHODS: Forty-one patients with MO were compared with age- and BMI-matched non-osteoporotic subjects after excluding overt systemic hypercortisolism (N = 41). Cortisol, cortisone and the respective tetrahydro-, 5α-tetrahydro- and total cortisol metabolites were analysed by GC-MS in 24 h urine. Apparent 11ß-hydroxysteroid dehydrogenase (11ß-HSD) enzyme activities, excretion of cortisol metabolites and calcium, and fractional urinary calcium excretion were assessed and related to BMD. RESULTS: Fractional and total urinary calcium excretion negatively correlated with BMD at all (P < 0.05) and at three of five (P < 0.05) measurement sites, respectively. While systemic cortisol was unchanged, apparent 11ß-HSD enzyme activity in MO patients (P < 0.01) suggested increased intracellular cortisol availability. Total and fractional urinary calcium excretion was higher, with apparent 11ß-HSD enzyme activities consistent with an enhanced intracellular cortisol availability (P < 0.05). CONCLUSION: Apparent 11ß-HSD enzyme activities consistent with increased intracellular cortisol availability correlated with urinary calcium loss and reduced bone mineral density in MO. The changes in 11ß-HSD activity were associated with both the fractional calcium excretion, suggesting altered renal calcium handling, and the absolute urinary calcium excretion. Both mechanisms could result in a marked bone calcium deficiency if insufficiently compensated for by intestinal calcium uptake.

Denosumab significantly increases DXA BMD at both trabecular and cortical sites: results from the FREEDOM study.

Denosumab is an approved therapy for postmenopausal women with osteoporosis at high or increased risk for fracture. In the FREEDOM study, denosumab reduced fracture risk and increased bone mineral density (BMD). We report the spine and hip dual-energy X-ray absorptiometry (DXA) BMD responses from the overall study of 7808 women and from a substudy of 441 participants in which more extensive spine and hip assessments as well as additional skeletal sites were evaluated. Significant BMD improvements were observed as early as 1 mo at the lumbar spine, total hip, and trochanter (all p<0.005 vs placebo and baseline). BMD increased progressively at the lumbar spine, total hip, femoral neck, trochanter, 1/3 radius, and total body from baseline to months 12, 24, and 36 (all p<0.005 vs placebo and baseline). BMD gains above the least significant change of more than 3% at 36 months were observed in 90% of denosumab-treated subjects at the lumbar spine and 74% at the total hip, and gains more than 6% occurred in 77% and 38%, respectively. In conclusion, denosumab treatment resulted in significant, early, and continued BMD increases at both trabecular and cortical sites throughout the skeleton over 36 mo with important gains observed in most subjects.

Human Bone Typing Using Quantitative Cone-Beam Computed Tomography.

INTRODUCTION: Bone typing is crucial to enable the choice of a suitable implant, the surgical technique, and the evaluation of the clinical outcome. Currently, bone typing is assessed subjectively by the surgeon. OBJECTIVE: The aim of this study is to establish an automatic quantification method to determine local bone types by the use of cone-beam computed tomography (CBCT) for an observer-independent approach. METHODS: Six adult human cadaver skulls were used. The 4 generally used bone types in dental implantology and orthodontics were identified, and specific Hounsfield unit (HU) ranges (grey-scale values) were assigned to each bone type for identification by quantitative CBCT (qCBCT). The selected scanned planes were labelled by nonradiolucent markers for reidentification in the backup/cross-check evaluation methods. The selected planes were then physically removed as thick bone tissue sections for in vitro correlation measurements by qCBCT, quantitative micro-computed tomography (micro-CT), and quantitative histomorphometry. RESULTS: Correlation analyses between the different bone tissue quantification methods to identify bone types based on numerical ranges of HU values revealed that the Pearson correlation coefficient of qCBCT with micro-CT and quantitative histomorphometry was R = 0.9 (P = .001) for all 4 bone types . CONCLUSIONS: We found that  qCBCT can reproducibly and objectively assess human bone types at implant sites.

The osteoporosis treatment gap in Switzerland between 1998 and 2018.

The annual number of patients treated for osteoporosis between 1998 and 2018 in Switzerland increased until 2008 and steadily decreased thereafter. With a continuously growing population at fracture risk exceeding an intervention threshold, the treatment gap has increased and the incidence of hip fractures has stopped declining in the past decade. INTRODUCTION: The existence of an osteoporosis treatment gap, defined as the percentage of patients at risk for osteoporotic fractures exceeding an intervention threshold but remaining untreated, is widely acknowledged. Between 1998 and 2018, new bone active substances (BAS) indicated for the treatment of osteoporosis became available. Whether and if so to what extent these new introductions have altered the treatment gap is unknown. METHODS: The annual number of patients treated with a BAS was calculated starting from single-drug unit sales. The number of patients theoretically eligible for treatment with a BAS was estimated based on four scenarios corresponding to different intervention thresholds (one based solely on a bone mineral density T score threshold and three FRAX-based thresholds) and the resulting annual treatment gaps were calculated. RESULTS: In Switzerland, the estimated number of patients on treatment with a BAS increased from 35,901 in year 1998 to 233,381 in year 2018. However, this number grew regularly since 1998, peaked in 2008, and steadily decreased thereafter, in timely coincidence with the launch of intravenous bisphosphonates and the RANKL inhibitor denosumab. When expressed in numbers of untreated persons at risk for osteoporotic fractures exceeding a given intervention threshold, the treatment gaps were of similar magnitude in 1998 (when the first BSAs just had become available) and 2018. There was a strong association, which does not imply causation, between the proportion of patients treated and hip fracture incidence. CONCLUSION: In Switzerland, the osteoporosis treatment gap has increased over the past decade. The availability of new BAS has not contributed to its decrease.

2D-3D reconstruction of the proximal femur from DXA scans: Evaluation of the 3D-Shaper software.

Introduction: Osteoporosis is currently diagnosed based on areal bone mineral density (aBMD) computed from 2D DXA scans. However, aBMD is a limited surrogate for femoral strength since it does not account for 3D bone geometry and density distribution. QCT scans combined with finite element (FE) analysis can deliver improved femoral strength predictions. However, non-negligible radiation dose and high costs prevent a systematic usage of this technique for screening purposes. As an alternative, the 3D-Shaper software (3D-Shaper Medical, Spain) reconstructs the 3D shape and density distribution of the femur from 2D DXA scans. This approach could deliver a more accurate estimation of femoral strength than aBMD by using FE analysis on the reconstructed 3D DXA. Methods: Here we present the first independent evaluation of the software, using a dataset of 77 ex vivo femora. We extend a prior evaluation by including the density distribution differences, the spatial correlation of density values and an FE analysis. Yet, cortical thickness is left out of this evaluation, since the cortex is not resolved in our FE models. Results: We found an average surface distance of 1.16 mm between 3D DXA and QCT images, which shows a good reconstruction of the bone geometry. Although BMD values obtained from 3D DXA and QCT correlated well (r 2 = 0.92), the 3D DXA BMD were systematically lower. The average BMD difference amounted to 64 mg/cm3, more than one-third of the 3D DXA BMD. Furthermore, the low correlation (r 2 = 0.48) between density values of both images indicates a limited reconstruction of the 3D density distribution. FE results were in good agreement between QCT and 3D DXA images, with a high coefficient of determination (r 2 = 0.88). However, this correlation was not statistically different from a direct prediction by aBMD. Moreover, we found differences in the fracture patterns between the two image types. QCT-based FE analysis resulted mostly in femoral neck fractures and 3D DXA-based FE in subcapital or pertrochanteric fractures. Discussion: In conclusion, 3D-Shaper generates an altered BMD distribution compared to QCT but, after careful density calibration, shows an interesting potential for deriving a standardized femoral strength from a DXA scan.

In major joint diseases the human synovium retains its potential to form repair cartilage.

The inner surface layer of human joints, the synovium, is a source of stem cells for the repair of articular cartilage defects. We investigated the potential of the normal human synovium to form novel cartilage and compared its chondrogenic capacity with that of two patient groups suffering from major joint diseases: young adults with femoro-acetabular impingement syndromes of the hip (FAI), and elderly individuals with osteoarthritic degeneration of the knee (OA). Synovial membrane explants of these three patient groups were induced in vitro to undergo chondrogenesis by growth factors: bone morphogenetic protein-2 (BMP-2) alone, transforming growth factor-ß1 (TGF-ß1) alone, or a combination of these two. Quantitative evaluations of the newly formed cartilages were performed respecting their gene activities, as well as the histochemical, immunhistochemical, morphological and histomorphometrical characteristics. Formation of adult articular-like cartilage was induced by the BMP-2/TGF-ß1 combination within all three groups, and was confirmed by adequate gene-expression levels of the anabolic chondrogenic markers; the levels of the catabolic markers remained low. Our data reveal that the chondrogenic potential of the normal human synovium remains uncompromised, both in FAI and OA. The potential of synovium-based clinical repair of joint cartilage may thus not be impaired by age-related joint pathologies.

A multi-stack registration technique to improve measurement accuracy and precision across longitudinal HR-pQCT scans.

BACKGROUND: Recent applications of high-resolution peripheral quantitative computed tomography (HR-pQCT) have demonstrated that changes in local bone remodelling can be quantified in vivo using longitudinal three-dimensional image registration. However, certain emerging applications, such as fracture healing and joint analysis, require larger multi-stack scan regions that can result in stack shift image artifacts. These artifacts can be detrimental to the accurate alignment of the bone structure across multiple timepoints. The purpose of this study was to establish a multi-stack registration protocol for evaluating longitudinal HR-pQCT images and to assess the accuracy and precision error in comparison with measures obtained using previously established three-dimensional longitudinal registration. METHODS: Three same day multi-stack HR-pQCT scans of the radius (2 stacks in length) and tibia (3 stacks in length) were obtained from 39 healthy individuals who participated in a previous reproducibility study. A fully automated multi-stack registration algorithm was developed to re-align stacks within a scan by leveraging slight offsets between longitudinal scans. Stack shift severity before and after registration was quantified using a newly proposed stack-shift severity score. The false discovery rate for bone remodelling events and precision error of bone morphology and micro-finite element analysis parameters were compared between longitudinally registered scans with and without the addition of multi-stack registration. RESULTS: Most scans (82 %) improved in stack alignment or maintained the lowest stack shift severity score when multi-stack registration was implemented. The false discovery rate of bone remodelling events significantly decreased after multi-stack registration, resulting in median false detection of bone formation and resorption fractions between 3.2 to 7.5 % at the radius and 3.4 to 5.3 % at the tibia. Further, precision error was significantly reduced or remained unchanged in all standard bone morphology and micro-finite element analysis parameters, except for total and trabecular cross-sectional areas. CONCLUSION: Multi-stack registration is an effective strategy for accurately aligning multi-stack HR-pQCT scans without modification of the image acquisition protocol. The algorithm presented here is a viable approach for performing accurate morphological analysis on multi-stack HR-pQCT scans, particularly for advanced application investigating local bone remodelling in vivo.

Precision of bone mechanoregulation assessment in humans using longitudinal high-resolution peripheral quantitative computed tomography in vivo.

Local mechanical stimuli in the bone microenvironment are essential for the homeostasis and adaptation of the skeleton, with evidence suggesting that disruption of the mechanically-driven bone remodelling process may lead to bone loss. Longitudinal clinical studies have shown the combined use of high-resolution peripheral quantitative computed tomography (HR-pQCT) and micro-finite element analysis can be used to measure load-driven bone remodelling in vivo; however, quantitative markers of bone mechanoregulation and the precision of these analyses methods have not been validated in human subjects. Therefore, this study utilised participants from two cohorts. A same-day cohort (n = 33) was used to develop a filtering strategy to minimise false detections of bone remodelling sites caused by noise and motion artefacts present in HR-pQCT scans. A longitudinal cohort (n = 19) was used to develop bone imaging markers of trabecular bone mechanoregulation and characterise the precision for detecting longitudinal changes in subjects. Specifically, we described local load-driven formation and resorption sites independently using patient-specific odds ratios (OR) and 99 % confidence intervals. Conditional probability curves were computed to link the mechanical environment to the remodelling events detected on the bone surface. To quantify overall mechanoregulation, we calculated a correct classification rate measuring the fraction of remodelling events correctly identified by the mechanical signal. Precision was calculated as root-mean-squared averages of the coefficient of variation (RMS-SD) of repeated measurements using scan-rescan pairs at baseline combined with a one-year follow-up scan. We found no significant mean difference (p < 0.01) between scan-rescan conditional probabilities. RMS-SD was 10.5 % for resorption odds, 6.3 % for formation odds, and 1.3 % for correct classification rates. Bone was most likely to be formed in high-strain and resorbed in low-strain regions for all participants, indicating a consistent, regulated response to mechanical stimuli. For each percent increase in strain, the likelihood of bone resorption decreased by 2.0 ± 0.2 %, and the likelihood of bone formation increased by 1.9 ± 0.2 %, totalling 38.3 ± 1.1 % of strain-driven remodelling events across the entire trabecular compartment. This work provides novel robust bone mechanoregulation markers and their precision for designing future clinical studies.

Prevalence and densitometric characteristics of incomplete distal renal tubular acidosis in men with recurrent calcium nephrolithiasis.

The aim of this study was to assess the prevalence of incomplete distal renal tubular acidosis (idRTA) in men with recurrent calcium nephrolithiasis and its potential impact on bone mineral density. We conducted a retrospective analysis of 150 consecutive, male idiopathic recurrent calcium stone formers (RCSFs), which had originally been referred to the tertiary care stone center of the University Hospital of Berne for further metabolic evaluation. All RCSFs had been maintained on a free-choice diet while collecting two 24-h urine samples and delivered second morning urine samples after 12 h fasting. Among 12 RCSFs with a fasting urine pH >5.8, a modified 3-day ammonium chloride loading test identified idRTA in 10 patients (urine pH >5.32, idRTA group). We matched to each idRTA subject 5 control subjects from the 150 RCSFs, primary by BMI and then by age, i.e., 50 patients, without any acidification defect (non-RTA group) for comparative biochemistry and dual energy X-ray absorptiometry (DEXA) analyses. The prevalence of primary idRTA among RCSFs was 6.7% (10/150). Patients with idRTA had significantly higher 2-h fasting and 24-h urine pH (2-h urine pH: 6.6 ± 0.4 vs. 5.2 ± 0.1, p = 0.001; 24-h urine pH: 6.1 ± 0.2 vs. 5.3 ± 0.3, p = 0.001), 24-h urinary calcium excretion (7.70 ± 1.75 vs. 5.69 ± 1.73 mmol/d, p = 0.02), but significantly lower 24-h urinary urea excretion (323 ± 53 vs. 399 ± 114 mmol/d, p = 0.01), urinary citrate levels (2.32 ± 0.82 vs. 3.01 ± 0.72 mmol/d, p = 0.04) and renal phosphate threshold normalized for the glomerular filtration rate (TmPO(4)/GFR: 0.66 ± 0.17 vs. 0.82 ± 0.21, p = 0.03) compared to non-RTA patients. No significant difference in bone mineral density (BMD) was found between idRTA and non-RTA patients for the lumbar spine (LS BMD (g/cm(2)): 1.046 ± 0.245 SD vs. 1.005 ± 0.119 SD, p = 0.42) or femoral neck (FN BMD (g/cm(2)): 0.830 ± 0.135 SD vs. 0.852 ± 0.127 SD). Thus, idRTA occurs in 1 in 15 male RCSFs and should be sought in all recurrent calcium nephrolithiasis patients. Bone mineral density, however, does not appear to be significantly affected by idRTA.

Recommendations for raloxifene use in daily clinical practice in the Swiss setting.

BACKGROUND/AIM: Raloxifene is the first selective estrogen receptor modulator that has been approved for the treatment and prevention of osteoporosis in postmenopausal women in Europe and in the US. Although raloxifene reduces the risk of invasive breast cancer in postmenopausal women with osteoporosis and in postmenopausal women at high risk for invasive breast cancer, it is approved in that indication in the US but not in the EU. The aim was to characterize the clinical profiles of postmenopausal women expected to benefit most from therapy with raloxifene based on published scientific evidence to date. METHODS: Key individual patient characteristics relevant to the prescription of raloxifene in daily practice were defined by a board of Swiss experts in the fields of menopause and metabolic bone diseases and linked to published scientific evidence. Consensus was reached about translating these insights into daily practice. RESULTS: Through estrogen agonistic effects on bone, raloxifene reduces biochemical markers of bone turnover to premenopausal levels, increases bone mineral density (BMD) at the lumbar spine, proximal femur, and total body, and reduces vertebral fracture risk in women with osteopenia or osteoporosis with and without prevalent vertebral fracture. Through estrogen antagonistic effects on breast tissue, raloxifene reduces the risk of invasive estrogen-receptor positive breast cancer in postmenopausal women with osteoporosis and in postmenopausal women at high risk for invasive breast cancer. Finally, raloxifene increases the incidence of hot flushes, the risk of venous thromboembolic events, and the risk of fatal stroke in postmenopausal women at increased risk for coronary heart disease. Postmenopausal women in whom the use of raloxifene is considered can be categorized in a 2 × 2 matrix reflecting their bone status (osteopenic or osteoporotic based on their BMD T-score by dual energy X-ray absorptiometry) and their breast cancer risk (low or high based on the modified Gail model). Women at high risk of breast cancer should be considered for treatment with raloxifene. CONCLUSION: Postmenopausal women between 50 and 70 years of age without climacteric symptoms with either osteopenia or osteoporosis should be evaluated with regard to their breast cancer risk and considered for treatment with raloxifene within the framework of its contraindications and precautions.

[Epidemiology and burden of osteoporosis in Switzerland]. / Epidemiologie und Stellenwert der Osteoporosein der Schweiz.

With increasing life expectancy and a growing proportion of elderly in the Swiss population, the burden of osteoporosis increases continuously. Every other woman and every fifth man aged 50 years or older will suffer an osteoportic fracture during her or his remaining lifetime. While the absolute number of hospitalizations for hip fractures has stabilized between year 2000 and 2007, the total number of hospitalizations for osteoporotic fractures has increased to 16'200 (+ 16 %) and 5'600 (+ 20 %) in women and men, respectively. Thus, osteoporosis continues belonging to those chronic diseases imposing the highest economic burden to the Swiss healthcare system, trend increasing. In addition, the risk of subsequent fractures as well as the adjusted mortality risk increases significantly after a first osteoporotic fracture. Should appropriate measures not be implemented in the near future, so will osteoporosis become one of the key challenges for the Swiss healthcare system within the coming years.