Interindividual differences contribute to variation in microbiota composition more than hormonal status: A prospective study.

Aims: Ovarian hormone deficiency is one of the main risk factors for osteoporosis and bone fractures in women, and these risks can be mitigated by menopausal hormone therapy. Recent evidence suggests that gut microbiota may link changes in estrogen levels and bone metabolism. This study was conducted to investigate the potential relationship between hormonal and bone changes induced by oophorectomy and subsequent hormonal therapy and shifts in gut microbiota composition. Methods: We collected 159 stool and blood samples in several intervals from 58 women, who underwent bilateral oophorectomy. Changes in fecal microbiota were assessed in paired samples collected from each woman before and after oophorectomy or the start of hormone therapy. Bacterial composition was determined by sequencing the 16S rRNA gene on Illumina MiSeq. Blood levels of estradiol, FSH, biomarkers of bone metabolism, and indices of low-grade inflammation were measured using laboratory analytical systems and commercial ELISA. Areal bone mineral density (BMD) of the lumbar spine, proximal femur, and femur neck was measured using dual-energy X-ray absorptiometry. Results: We found no significant changes in gut microbiota composition 6 months after oophorectomy, despite major changes in hormone levels, BMD, and bone metabolism. A small decrease in bacterial diversity was apparent 18 months after surgery in taxonomy-aware metrics. Hormonal therapy after oophorectomy prevented bone loss but only marginally affected gut microbiota. There were no significant differences in ß-diversity related to hormonal status, although several microbes (e.g., Lactococcus lactis) followed estrogen levels. Body mass index (BMI) was the most significantly associated with microbiota variance. Microbiota was not a suitable predictive factor for the state of bone metabolism. Conclusions: We conclude that neither the loss of estrogens due to oophorectomy nor their gain due to subsequent hormonal therapy is associated with a specific gut microbiota signature. Sources of variability in microbiota composition are more related to interindividual differences than hormonal status.

Treatment of postmenopausal osteoporosis patients with teriparatide for 24 months reverts forming bone quality indices to premenopausal healthy control values.

Postmenopausal osteoporosis (PMOP) therapies are frequently evaluated by bone mineral density (BMD) gains against patients receiving placebo (calcium and vitamin D supplementation, a mild bone turnover-suppressing intervention), which is not equivalent to either healthy or treatment-naive PMOP. The aim of the present observational study was to assess the effects of TPTD treatment in PMOP (20 µg, once daily) at 6 (TPTD 6m; n = 28, age 65 ± 7.3 years), and 24 (TPTD 24m; n = 32, age 67.4 ± 6.15 years) months on bone quality indices at actively forming trabecular surfaces (with fluorescent double labels). Data from the TPTD-treated PMOP patients were compared with those in healthy adult premenopausal women (HC; n = 62, age 40.5 ± 10.6 years), and PMOP receiving placebo (PMOP-PLC; n = 94, age 70.6 ± 4.5 years). Iliac crest biopsies were analyzed by Raman microspectroscopy at three distinct tissue ages: mid-distance between the second label and the bone surface, mid-distance between the two labels, and 1 µm behind the first label. Mineral to matrix ratio (MM), mineral maturity/crystallinity (MMC), tissue water (TW), glycosaminoglycan (GAGs), and pyridinoline (Pyd) content were determined. Outcomes were compared by ANCOVA with subject age and tissue age as covariates, and health status as a fixed factor, followed by Sidak's post-hoc testing (significance assigned to p < 0.05). Both TPTD groups increased MM compared to PMOP-PLC. While TPTD 6m had values similar to HC, TPTD 24m had higher values compared to either HC or TPTD 6m. Both TPTD groups had lower MMC values compared to PMOP-PLC and similar to HC. TPTD 6m patients had higher TW content compared to HC, while TPTD 24m had values similar to HC and lower than either PMOP-PLC or TPTD 6m. Both TPTD groups had lower GAG content compared to HC group, while TPTD 6m had higher values compared to PMOP-PLC. Finally, TPTD 6m patients had higher Pyd content compared to HC and lower compared to PMOP-PLC, while TPTD 24m had lower values compared to PMOP-PLC and TPTD 6m, and similar to HC group. The results of the present study indicate that effects of TPTD on forming trabecular bone quality indices depend on treatment duration. At the recommended length of 24 m, TPTD restores bone mineral and organic matrix quality indices (MMC, TW, Pyd content) to premenopausal healthy (HC) levels.

Possibilities and limits of using gyroscopic sensors in the diagnosis of progression of osteoarthritis and femoroacetabular impingement syndrome.

Osteoarthritis is the most common type of degenerative joint disease and affects millions of people. In this paper, we propose a non-obtrusive and straightforward method to assess the progression of osteoarthritis. In standard medicine praxis, osteoarthritis is observed with X-rays. In this study, we use widely available wearable sensors with gyroscopes to make the observation. Two novel methods are proposed for gyroscope data processing. A small-scale study has shown that these methods can be used to monitor osteoarthritis's progression, and to differentiate between healthy subjects and subjects with femoroacetabular impingement syndrome.

Menopausal Transition: Prospective Study of Estrogen Status, Circulating MicroRNAs, and Biomarkers of Bone Metabolism.

Objective: Osteoporosis is associated with an impaired balance between bone resorption and formation, which in turn leads to bone loss and fractures. Many recent studies have underlined the regulatory role of microRNAs (miRNAs) in bone remodeling processes and their potential as biomarkers of osteoporosis. The purpose of this study was to prospectively examine the association of circulating miRNAs and bone biomarkers with estrogen status in women before and after oophorectomy, as well as in oophorectomized women on estrogen therapy. Methods: In this prospective study, we included 11 women before oophorectomy and hysterectomy and at 201 ± 24 days after the surgery. Another 11 women were evaluated 508 ± 127 days after oophorectomy and hysterectomy and after an additional 203 ± 71 days of estradiol treatment. Serum miRNAs were profiled by sequencing. Estrogen status and biomarkers of bone metabolism were quantified. Bone mineral density was assessed in the lumbar spine. Results: Our analysis revealed 17 miRNAs associated with estrogen levels. Of those miRNAs that were upregulated with estrogen deficiency and downregulated after estrogen therapy, miR-422a correlated with serum beta-carboxy-terminal type I collagen crosslinks (ß-CTX) and procollagen 1 N-terminal propeptide (P1NP); and miR-1278 correlated with serum ß-CTX, P1NP, osteocalcin, sclerostin, and Dickkopf-1(Dkk1). In contrast, we found an inverse association of miR-24-1-5p with estrogen status and a negative correlation with serum ß-CTX, P1NP, osteoprotegerin, and sclerostin levels. Conclusion: The reported miRNAs associated with estrogen status and bone metabolism could be potential biomarkers of bone pathophysiology and would facilitate studies on the prevention of postmenopausal osteoporosis. Our findings require validation in an extended cohort.

S100A4 is elevated in axial spondyloarthritis: a potential link to disease severity.

BACKGROUND: S100A4 is a member of calcium binding S100 protein family well known for its role in cancer progression and metastasis. Nevertheless, S100A4 also serves as a negative regulator of bone formation. Dickkopf-1 (DKK-1), marker of bone remodelling, is also implicated in the process of syndesmophyte formation in ankylosing spondylitis. The aim of our study was to evaluate plasma levels of S100A4 in patients with axial spondyloarthritis and to determine the potential association of S100A4 with disease severity, clinical manifestations and with bone changes in a cross-sectional study. METHODS: Fifty-eight patients with axial spondyloarthritis and 40 healthy controls were studied. Biological samples were analysed for S100A4 and Dickkopf-1. Disease activity was assessed according to the Bath Ankylosing Spondylitis Disease Activity Index. C-reactive protein (CRP) was used as a marker of inflammation. Radiographic damage was assessed using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). RESULTS: The plasma levels of S100A4 were significantly higher in patients with axial spondyloarthritis compared to heathy controls (p < 0.0001). The levels of S100A4 were higher in early stages of the disease and lower in patients with the presence of syndesmophytes (p = 0.009). Furthermore, we found weak but significant inverse correlation of plasma S100A4 with the mSASSS (r = - 0.363, p = 0.030). Levels of S100A4 were negatively associated with disease duration (r = - 0.404, p = 0.002) and positively with Dickkopf-1 binding capacity (r = 0.312, p = 0.023). CONCLUSIONS: This is the first study showing elevated circulating levels of S100A4 in patients with axial spondyloarthritis, particularly in early stages of the disease prior to spinal involvement, and its significantly lower levels in patients with syndesmophytes. The role of S100A4 in the pathogenesis of axial spondyloarthritis can be suggested.

Update on Menopausal Hormone Therapy for Fracture Prevention.

PURPOSE OF REVIEW: The goal of the review is to assess the appropriateness of menopausal hormone therapy (MHT) for the primary prevention of bone loss in women at elevated risk in the early years after menopause. RECENT FINDINGS: Estrogen alone or combined with progestin to protect the uterus from cancer significantly reduces the risk of osteoporosis-related fractures. MHT increases type 1 collagen production and osteoblast survival and maintains the equilibrium between bone resorption and bone formation by modulating osteoblast/osteocyte and T cell regulation of osteoclasts. Estrogens have positive effects on muscle and cartilage. Estrogen, but not antiresorptive therapies, can attenuate the inflammatory bone-microenvironment associated with estrogen deficiency. However, already on second year of administration, MHT is associated with excess breast cancer risk, increasing steadily with duration of use. MHT should be considered in women with premature estrogen deficiency and increased risk of bone loss and osteoporotic fractures. However, MHT use for the prevention of bone loss is hindered by increase in breast cancer risk even in women younger than 60 years old or who are within 10 years of menopause onset.

Low-Cost Radon Detector with Low-Voltage Air-Ionization Chamber.

This paper describes the design of a low-cost radon detector that can easily be fabricated in large quantities for the purposes of earthquake prediction. The described detector can also be used for monitoring radon levels in houses because high radon levels pose a great health risk. A very simple air-ionization chamber for alpha particles was used, considering the experimental results. Chamber current-sensing circuitry is also suggested, and an Internet of Things (IoT) sensor grid is described. The main advantages of this detector are the low cost, low power consumption, and complete elimination of high-voltage power sources. The minimum detectable activity achieved with the proposed detector for one measurement was around 50 Bq · m - 3 , with time of measurement comparable to that featured on commercial devices, while the price of the described detector is one order of magnitude lower.

Current vitamin D status in European and Middle East countries and strategies to prevent vitamin D deficiency: a position statement of the European Calcified Tissue Society.

Vitamin D deficiency (serum 25-hydroxyvitamin D (25(OH)D) <50 nmol/L or 20 ng/mL) is common in Europe and the Middle East. It occurs in <20% of the population in Northern Europe, in 30-60% in Western, Southern and Eastern Europe and up to 80% in Middle East countries. Severe deficiency (serum 25(OH)D <30 nmol/L or 12 ng/mL) is found in >10% of Europeans. The European Calcified Tissue Society (ECTS) advises that the measurement of serum 25(OH)D be standardized, for example, by the Vitamin D Standardization Program. Risk groups include young children, adolescents, pregnant women, older people (especially the institutionalized) and non-Western immigrants. Consequences of vitamin D deficiency include mineralization defects and lower bone mineral density causing fractures. Extra-skeletal consequences may be muscle weakness, falls and acute respiratory infection, and are the subject of large ongoing clinical trials. The ECTS advises to improve vitamin D status by food fortification and the use of vitamin D supplements in risk groups. Fortification of foods by adding vitamin D to dairy products, bread and cereals can improve the vitamin D status of the whole population, but quality assurance monitoring is needed to prevent intoxication. Specific risk groups such as infants and children up to 3 years, pregnant women, older persons and non-Western immigrants should routinely receive vitamin D supplements. Future research should include genetic studies to better define individual vulnerability for vitamin D deficiency, and Mendelian randomization studies to address the effect of vitamin D deficiency on long-term non-skeletal outcomes such as cancer.

Serum 25-hydroxy-vitamin D and the risk of fractures in the teriparatide versus risedronate VERO clinical trial.

PURPOSE: Using data from the 2-year, randomized, double-dummy VERO trial, we examined the changes in 25-hydroxy-vitamin D (25[OH]D) concentrations over time, and whether the fracture risk reduction of teriparatide versus risedronate varies by baseline 25(OH)D sufficiency category. METHODS: Postmenopausal women with established osteoporosis received subcutaneous daily teriparatide 20 µg or oral weekly risedronate 35 mg, with concomitant 500-1000 mg of elemental calcium and 400-800 IU/day of vitamin D supplements. Fracture endpoints were analyzed by predefined subgroups of 25(OH)D insufficient and sufficient patients. Heterogeneity of the treatment effect on fractures was investigated by logistic and Cox proportional hazards regression models. RESULTS: At baseline, mean serum 25(OH)D was 31.9 ng/mL in the teriparatide group and 31.5 ng/mL in the risedronate group, and 16.8% and 17.9% of patients, respectively, were 25(OH)D insufficient. At month 6, the mean serum 25(OH)D concentration decreased in teriparatide-treated patients to 24.5 ng/mL (by approximately 23%) but remained relatively constant in risedronate-treated patients (32.2 ng/mL) (p < 0.001). Proportions of 25(OH)D insufficient patients at month 6 were 26.7% and 5.6%, respectively (p < 0.001). The risk reduction with teriparatide versus risedronate for any of the fracture endpoints did not significantly differ between subgroups by 25(OH)D sufficiency status at baseline, with nonsignificant (p > 0.1) treatment-by-25(OH)D interactions in all fracture analyses. CONCLUSIONS: Serum 25(OH)D concentration decreases during teriparatide treatment. Fracture risk reduction with teriparatide versus risedronate did not significantly differ between the two groups of patients defined by baseline 25(OH)D. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01709110 EudraCT Number: 2012-000123-41.

Teriparatide Treatment Increases Mineral Content and Volume in Cortical and Trabecular Bone of Iliac Crest: A Comparison of Infrared Imaging With X-Ray-Based Bone Assessment Techniques.

Teriparatide increases bone mass primarily through remodeling of older or damaged bone and abundant replacement with new mineralizing bone. This post hoc analysis investigated whether dual-energy X-ray absorptiometric (DXA) areal bone mineral density (aBMD) measurement adequately reflects changes of mineral and organic matrix content in cortical and trabecular bone. Paired biopsies and aBMD measurements were obtained before and at end of 2 years of teriparatide treatment from postmenopausal women with osteoporosis who were either alendronate pretreated (mean, 57.5 months) or osteoporosis-treatment naive. Biopsies were assessed by micro-computed tomography (µCT) to calculate mean cortical width (Ct.Wi), cortical area (Ct.Ar), and trabecular bone volume fraction (BV/TV). Fourier transformed infrared imaging (pixel size ∼6.3 × 6.3 µm2 ) was utilized to calculate mineral and organic matrix density (mean absorption/pixel), as well as total mineral and organic contents of cortical and cancellous compartments (sum of all pixels in the compartment). Effect of pretreatment over time was analyzed using mixed model repeated measures. µCT derived Ct.Wi and BV/TV increased, accompanied by similar increases in the overall mineral contents of their respective bone compartments. Mineral density did not change. Marked increases in the total content of both mineral and organic matrix associated with volumetric growth in both compartments consistently exceeded those of aBMD. Increases in organic matrix exceeded increases in mineral content in both cortical and trabecular compartments. For percent changes, only change in Ct.Wi correlated to change in femoral neck aBMD (r = .38, p = 0.043), whereas no other significant correlations of Ct.Wi or BV/TV with lumbar spine, total hip, or femoral neck aBMD were demonstrable. These data indicate that 2 years of teriparatide treatment leads to an increased bone organic matrix and mineral content in the iliac crest. The magnitude of these increases in the iliac crest were not detected with conventional aBMD measurements at other skeletal sites. © 2018 American Society for Bone and Mineral Research.

[Osteoporosis and quality of bone]. / Osteoporóza a kvalita kostní hmoty.

The risk of osteoporotic fracture is determined collectively by bone mineral density, bone mass, architecture and properties of the mineral and organic matrix composite. Changes in these distinct aspects of quality of bone with age, estrogen deficiency, diseases leading to increased risk of fracture and differential mode of action of antiresorptive and bone anabolic treatments have to be considered in clinical therapeutic strategies. In patients at high risk of low impact fracture, sequential therapy switching to antiresorptives after patients have an adequate response to 2 years teriparatide may be the optimal strategy of long term therapy.Key words: aging - bone quality - osteoporosis - prevention - therapy.

Effects of Teriparatide Compared with Risedronate on the Risk of Fractures in Subgroups of Postmenopausal Women with Severe Osteoporosis: The VERO Trial.

The 2-year, randomized, double-blind, active-controlled fracture endpoint VERO study included postmenopausal women with established osteoporosis, who had at least 2 moderate or 1 severe baseline vertebral fractures (VFx), and bone mineral density (BMD) T-score ≤-1.5. Patients were treated with either s.c. daily teriparatide 20 µg or oral weekly risedronate 35 mg. As previously reported, the risk of new VFx and clinical fractures (a composite of clinical VFx and nonvertebral fragility fractures [NVFFx]) was statistically significantly reduced with teriparatide compared with risedronate. Here we present the prospectively planned subgroup analyses of fracture data across subgroups, which were predefined by the following baseline characteristics: age, number and severity of prevalent VFx, prevalent nonvertebral fractures (NVFx), glucocorticoid use, prior osteoporosis drugs, recent bisphosphonate use, clinical VFx in the year before study entry, and baseline BMD. Heterogeneity of the treatment effect on the primary endpoint (new VFx), and the four key secondary endpoints (including clinical fractures and NVFFx) were investigated by logistic and Cox proportional hazards regression models. A total of 1360 women were randomized and treated (680 per group). Mean age was 72.1 years, mean (SD) number of prevalent VFx was 2.7 (2.1), 55.4% had a BMD T-score <-2.5, 36.5% had a recent clinical VFx, 28.3% had a prior major NVFx, 43.2% were osteoporosis drug-naïve, 39.3% were recent bisphosphonate users, and 9.3% were taking glucocorticoids at a prednisone-equivalent dose of >5 mg/d. For most fracture endpoints, the risk reduction of teriparatide versus risedronate did not significantly differ in any of the subgroups analyzed (treatment-by-subgroup interaction p > 0.1), with most subgroups mirroring results from the total study population. In conclusion, in postmenopausal women with severe osteoporosis, the antifracture efficacy of teriparatide compared with risedronate was consistent in a wide range of patient settings, including treatment-naïve and previously treated patients. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.

Secondary fracture prevention in hip fracture patients requires cooperation from general practitioners.

Despite individual recommendations on osteoporosis management in patients after hip fracture surgery, addressed by orthopedic surgeons to Czech general practitioners, the patients remained undiagnosed and untreated because of provider-level barriers to post-fracture secondary prevention. PURPOSE: The goal of the study was to assess whether an individual recommendation on osteoporosis treatment addressed to a hip fracture patient's GP would lead to better osteoporosis management. METHODS: Two groups of patients who suffered hip fractures and were treated at the Orthopedic Department were evaluated. In 111 patients, general recommendations on osteoporosis treatment and fracture prevention were provided in a discharge report addressed to the GP. In the second group, 96 patients were provided individually with a detailed written set of recommendations on osteoporosis examination, treatment, and fracture prevention, which was also provided in the discharge report. A questionnaire to assess the provided care was mailed to the patients 5.3 ± 1.2 months of discharge. Those patients who did not return the questionnaires were contacted by phone. RESULTS: The questionnaires were received from 44% and 49% of patients from the general and detailed recommendation groups, respectively. Along with the phone call, we were able to contact 78 (70.3%) and 68 (70.8%) patients from the general and detailed recommendation groups, respectively. GPs secured osteoporosis evaluation in 14.6% of the patients. Calcium supplementation and vitamin D supplementation were newly provided in 42.7 and 36.4% of the patients, respectively. Anti-resorptive therapy was newly provided in 8.3% of the patients. No significant differences between the groups were observed in osteoporosis evaluation, calcium and vitamin D supplementation, and anti-osteoporosis treatments. Out of 207 patients, further examination or treatment was requested by 45 patients (21.7%); 75 patients (36.2%) declared no interest in further care. CONCLUSION: Recommendations on osteoporosis management addressed to Czech GPs after surgical fracture management had little effect on treatment. As the anti-osteoporotic preparations can only be prescribed by specialists, the availability of necessary examinations and treatment is limited by the motivation of GPs. Consequently, the implementation of Fracture Liaison Services to help close the care gap may be limited in the absence of participation by Czech GPs.

How General Practitioners and Their Patients Adhere to Osteoporosis Management: A Follow-Up Survey among Czech General Practitioners.

Introduction: General practitioners (GPs) are key participants in osteoporosis (OP) management. The aim was to evaluate their adherence to lege artis management of the disease, potential barriers, and to discuss differences observed in comparison with the baseline survey carried out in 2007; the focus was on secondary prevention. Methods: On behalf of two professional associations, 2-round postal survey among randomly selected GPs (>1/4 of all Czech GPs) was performed in 2014. The questionnaire covered areas concerning GP's role in the fight against OP, knowledge about OP, management of OP-related fractures, barriers to the management of OP, system- and patient-related in particular, and availability and use of information sources. Results: The overall questionnaire return rate was 37% (551 respondents); mean age of the respondents was 53 year (37% men). The GP's role in the treatment of OP was rated as essential in 28 and 37% of men and women, respectively (P = 0.012). The guideline for diagnosis and treatment of OP for GPs was considered accessible by 92% of respondents. As much as 60% of the respondents were adherent to the guideline, i.e., used it repeatedly. The knowledge of several risk factors was very good, however, recommended daily intake of calcium was stated correctly by only 41% of respondents, and daily intake of vitamin D by only 40%. Three quarters reported active steps after a fracture: referral to a specialist, life-style recommendations, prescription of calcium/vitamin D supplements. Half of the respondents focus on fall prevention. System-related barriers, such as lack of possibility to prescribe selected drugs (61%) and financial limits set by health insurance company (44%) were most frequently reported. Patient-related barriers were also common, patient's non-adherence (reported by 29%) and patient's reluctance to go to a specialist (18%). Conclusion: GPs adhered to OP management more than in 2007. Knowledge of risk factors and involvement in post-fracture care was relatively high. Compared to baseline survey, patient-related barriers, patient non-adherence in particular, were more common. Prescribing conditions are still an important issue. Among GPs, education should be focused on calcium and vitamin D intake, doses, sources, and supplements.

Effect of Teriparatide or Risedronate in Elderly Patients With a Recent Pertrochanteric Hip Fracture: Final Results of a 78-Week Randomized Clinical Trial.

We present final results of a study comparing teriparatide 20 µg every day (QD) with risedronate 35 mg once per week (QW) started within 2 weeks after surgery for a pertrochanteric hip fracture. Patients with BMD T-score ≤ -2.0 and 25OHD ≥9.2 ng/mL were randomized to receive 26-week double-dummy treatment plus calcium and vitamin D, followed by 52-week open-label treatment with the same assigned active drug. Primary endpoint was change from baseline in lumbar spine (LS) BMD at 78 weeks. Secondary and exploratory endpoints were change in BMD at the proximal femur, function, hip pain (Charnley score and 100 mm Visual Analog Scale [VAS]), quality of life (Short Form-36), radiology outcomes, and safety. Data were analyzed with mixed models for repeated measures (MMRM) and logistic regression. Totally, 224 patients were randomized; 171 (teriparatide: 86) contributed to the efficacy analyses (mean ± SD age: 77 ± 7.7 years, 77% females). Mean baseline LS, femoral neck (FN), and total hip (TH) T-scores were -2.16, -2.63, and -2.51, respectively. At 78 weeks, BMD increased significantly more with teriparatide compared to risedronate at the LS (+11.08% versus +6.45%; p < 0.001) and FN (+1.96% versus -1.19%; p = 0.003), with no significant between-group difference in TH BMD. Timed up-and-go (TUG) test was significantly faster with teriparatide at 6, 12, 18, and 26 weeks (differences: -3.2 to -5.9 s; p = 0.045 for overall difference). Hip pain during TUG test by 100 mm VAS was significantly lower with teriparatide at 18 weeks (adjusted difference: -11.3 mm, p = 0.033; -10.0 and -9.3 mm at 12 and 26 weeks, respectively; p = 0.079 for overall difference). Other secondary and exploratory outcomes were not different. Teriparatide group showed two new hip fractures versus seven with risedronate (p = 0.171) and more frequent hypercalcemia and hyperuricemia. In conclusion, 78-week treatment with teriparatide showed significantly greater increases in LS and FN BMD, less pain, and a faster TUG test versus risedronate. © 2016 American Society for Bone and Mineral Research.

Focal osteoporosis defects play a key role in hip fracture.

BACKGROUND: Hip fractures are mainly caused by accidental falls and trips, which magnify forces in well-defined areas of the proximal femur. Unfortunately, the same areas are at risk of rapid bone loss with ageing, since they are relatively stress-shielded during walking and sitting. Focal osteoporosis in those areas may contribute to fracture, and targeted 3D measurements might enhance hip fracture prediction. In the FEMCO case-control clinical study, Cortical Bone Mapping (CBM) was applied to clinical computed tomography (CT) scans to define 3D cortical and trabecular bone defects in patients with acute hip fracture compared to controls. Direct measurements of trabecular bone volume were then made in biopsies of target regions removed at operation. METHODS: The sample consisted of CT scans from 313 female and 40 male volunteers (158 with proximal femoral fracture, 145 age-matched controls and 50 fallers without hip fracture). Detailed Cortical Bone Maps (c.5580 measurement points on the unfractured hip) were created before registering each hip to an average femur shape to facilitate statistical parametric mapping (SPM). Areas where cortical and trabecular bone differed from controls were visualised in 3D for location, magnitude and statistical significance. Measures from the novel regions created by the SPM process were then tested for their ability to classify fracture versus control by comparison with traditional CT measures of areal Bone Mineral Density (aBMD). In women we used the surgical classification of fracture location ('femoral neck' or 'trochanteric') to discover whether focal osteoporosis was specific to fracture type. To explore whether the focal areas were osteoporotic by histological criteria, we used micro CT to measure trabecular bone parameters in targeted biopsies taken from the femoral heads of 14 cases. RESULTS: Hip fracture patients had distinct patterns of focal osteoporosis that determined fracture type, and CBM measures classified fracture type better than aBMD parameters. CBM measures however improved only minimally on aBMD for predicting any hip fracture and depended on the inclusion of trabecular bone measures alongside cortical regions. Focal osteoporosis was confirmed on biopsy as reduced sub-cortical trabecular bone volume. CONCLUSION: Using 3D imaging methods and targeted bone biopsy, we discovered focal osteoporosis affecting trabecular and cortical bone of the proximal femur, among men and women with hip fracture.

[Raloxifene - an unexploited possibility of prevention and treatment of postmenopausal osteoporosis]. / Raloxifen - nevyuzitá moznost prevence a lécby postmenopauzální osteoporózy.

Long-term estrogen deficiency after menopause is responsible for different disorders, which not only make the quality of life in the older age worse but also are the major causes of womens mortality. It is especially the case for cardiovascular disease and osteoporosis. Aim of this review is to point at efficacy of raloxifene (a selective estrogen receptor modulator) in the long-term care of the women in their non-reproductive period of life, and namely in prevention and treatment of postmenopausal osteoporosis.Key words: bone turnover - breast cancer - postmenopausal osteoporosis - prevention - raloxifene.

[Osteoporosis in men]. / Osteoporóza u muzu.

The health burden of osteoporosis in men is expected to increase with an aging population and increasing life expectancy. Both hip and vertebral fractures are associated with increased morbidity and mortality in men. The clinical evaluation, measurement of bone mineral density using dual-energy X-ray absorptiometry, laboratory tests and fracture risk assessment is now recognized as the standard for diagnosis of osteoporosis in males, and a preferred approach to guide treatment decisions. Clinical trials have demonstrated efficacy of several treatment options available for men with osteoporosis. Moreover, clinical interventions to improve physical performance could also reduce the risk of future fractures.

Effects of Teriparatide Compared with Risedronate on Recovery After Pertrochanteric Hip Fracture: Results of a Randomized, Active-Controlled, Double-Blind Clinical Trial at 26 Weeks.

BACKGROUND: Osteoporosis drugs might affect fracture-healing. We therefore studied the effects of teriparatide in comparison with risedronate on recovery after pertrochanteric hip fractures. METHODS: The study was a randomized, multicenter, active-controlled, 78-week trial comparing teriparatide (20 µg/day) with risedronate (35 mg/week) initiated within 2 weeks after fixation of a low-trauma pertrochanteric hip fracture (AO/OTA 31-A1 or 31-A2). The main inclusion criteria were a bone mineral density T-score of ≤-2.0 and 25-OH-vitamin D of ≥9.2 ng/mL. During the first 26 weeks, patients received study medication with oral or injectable placebo plus calcium and vitamin D in a double-blinded fashion. Secondary (Timed Up-and-Go [TUG] test, hip pain, Short Form [SF]-36 health status, and safety) and exploratory (radiographic outcomes and ability to walk) 26-week end points are reported. RESULTS: Of the 224 patients who were randomized, 171 (86 teriparatide, 85 risedronate) were included in the analysis. The mean age was 77 ± 8 years, 77% were female, and 26% had a prior history of low-trauma fracture. The teriparatide group completed the TUG test in a shorter time at 6, 12, 18, and 26 weeks (differences of -5.7, -4.4, -3.1, and -3.1 seconds, respectively; p = 0.021 for the overall difference). They also reported less pain on a visual analog scale immediately after the TUG test at 12 and 18 weeks (adjusted absolute differences of 10.6 and 11.9 mm, respectively; p < 0.05). There were no significant between-group differences in the SF-36 score, Charnley hip pain score, ability to walk, or use of walking aids during follow-up. Radiographic healing at 6, 12, and 26 weeks, mechanical failure of the implant (teriparatide, 7; risedronate, 8), loss of reduction (teriparatide, 2; risedronate, 4), and nonunion (0 cases) were not significantly different. Mild hypercalcemia and hyperuricemia were more frequent with teriparatide. CONCLUSIONS: Teriparatide was associated with less pain and a shorter time to complete the TUG test between 6 and 26 weeks compared with risedronate. Other fracture-recovery outcomes were similar. The results should be interpreted with caution as these were secondary end points. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Serum and bone pentosidine in patients with low impact hip fractures and in patients with advanced osteoarthritis.

BACKGROUND: Femoral neck fractures are a common occurrence in patients suffering from osteoporosis, while intracapsular hip fracture is rare in cases of osteoarthritis of the hip. Previous histomorphometric studies have emphasized the association between bone microarchitecture and the risk of low-impact fractures in osteoarthritis and osteoporosis patients. However, the strength of bone material is also a function of composition of organic bone matrix. In order to compare tissue material properties in these two clinical conditions, serum and bone pentosidine, a non-enzymatic collagen crosslinking element, was measured in patients who suffered a low-impact fracture, and in patients with advanced osteoarthritis. METHODS: The patient population consisted of 70 patients who underwent hemiarthroplasty surgery for a femoral neck fracture, and 41 patients with advanced hip joint osteoarthritis without a history of low- impact fracture, who were indicated for total hip joint replacement. Pentosidine content was analyzed in bone samples and in serum obtained from fracture and osteoarthritis patients using high performance liquid chromatography. RESULTS: Serum and bone concentrations of pentosidine were higher in subjects with hip fractures compared with osteoarthritis after adjustment for age, sex, weight, serum creatinine, and diabetes. A significant positive correlation was found between bone and serum pentosidine in fractured cases. A comparable relationship was also demonstrated for pentosidine levels in serum and bone relative to differentiation of fracture and osteoarthritis cases. CONCLUSIONS: Serum pentosidine can be considered a potential biomarker for identification of subjects with impaired bone quality and bone strength.