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.

[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.

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.

[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.

[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.

The association between lean mass and bone mineral content in the high disease activity group of adult patients with juvenile idiopathic arthritis.

BACKGROUND: The study is aimed to evaluate body composition and bone status in adolescent and adult patients with active juvenile idiopathic arthritis (JIA) untreated with tumor necrosis factor alpha inhibitors. METHODS: Adult patients (12 male and 19 female) with active JIA and 84 healthy age- and gender- matched controls were enrolled into the study. Body composition (tissue mass in grams, lean mass, fat mass and bone mineral content as a fraction of tissue mass) and areal bone mineral density parameters (aBMD) at the lumbar spine, proximal femur, femoral neck, distal radius and total body were assessed using dual energy x-ray absorptiometry (DXA), and correlated with clinical characteristics of the disease and physical performance tests. Disease activity was assessed using high-sensitivity C-reactive protein (hsCRP) and disease activity score 28 (DAS 28). Differences between the groups were tested by t-test, and One-way ANOVA. Correlations were assessed using the Pearson correlation coefficients and multiple linear regression analysis. Significances were counted at the 0.05 level. RESULTS: In patients with clinically active JIA (DAS 28, 6.36 ± 0.64, hsCRP, 18.36 ± 16.95 mg/l), aBMD at all measured sites, bone mineral content (BMC) and lean mass were reduced, and fat mass was increased as compared with healthy controls. Significant negative correlations were observed between BMC and disease duration, use of glucocorticoids (GCs), and fat mass, respectively. A positive correlation was found between BMC and lean mass, and between the body fat fraction and the use of GCs. Using multiple linear regression analysis, lean mass was the only significant predictor of BMC of total body both in men and women, and of BMC of legs (only in men). Lean mass was also the only predicting factor of total proximal femur BMD and femoral neck BMD. No significant correlations have been determined among the body composition parameters and DAS 28 or hsCRP endpoints. CONCLUSIONS: In adult patients with long-term active JIA, lean mass was the main determining factor of total body and leg BMC, and total proximal femur and femoral neck aBMD.

Acute effects of glucocorticoids on serum markers of osteoclasts, osteoblasts, and osteocytes.

The aim of this study was to investigate the acute effects of oral glucocorticoids in doses used in clinical practice on biochemical indices of the function of osteoclasts, osteoblasts, and osteocytes. In 17 adult patients suffering from various medical pathologies requiring systemic steroid therapy that were never before treated with glucocorticoids, glucocorticoid treatment was initiated (mean prednisolone equivalent dose of 23.1 ± 12.7 mg/day, range 10-50). Fasting morning serum concentrations of osteocalcin (OC), amino-terminal propeptide of type I procollagen (PINP), type 1 collagen cross-linked C-telopeptide (ßCTX), soluble receptor activator of nuclear factor kappaB ligand (sRANKL), osteoprotegerin (OPG), sclerostin, Dickkopf-1 (Dkk-1), and high-sensitivity C-reactive protein (hsCRP) were measured at baseline and on three consecutive days. Significant reductions in serum OC, PINP, OPG, sclerostin, and hsCRP were observed during 96 h of glucocorticoid administration, while serum ßCTX showed a significant percentual increase. A significant positive correlation was found between serum concentrations of Dkk-1 and ßCTX after 96 h of treatment with glucocorticoids. A significant drop in serum sclerostin, OPG, and OC observed in this study may reflect the rapid glucocorticoid-induced apoptosis of osteocytes.

Strontium ranelate: in search for the mechanism of action.

Strontium ranelate is a medicine with evidenced effects on the risk of fractures. The heterogeneity of strontium distribution in bone, quality of bone mineral crystals in young bone packets on bone surfaces formed during strontium ranelate administration, and activation of the calcium sensing receptor may, at least partially, explain the beneficial effects of SrR on reducing the risk of fractures. In this review, the concept of the dual action of strontium ranelate is also discussed. However, sufficient evidence for the bone anabolic effect of SrR does not exist in humans. The knowledge of the mechanism of action of SrR is important not only for the explanation of the effects of SrR upon the skeleton, but also for the safety of treatment for other tissues.

Bone status in adults with early-onset juvenile idiopathic arthritis following 1-year anti-TNFα therapy and discontinuation of glucocorticoids.

Juvenile idiopathic arthritis (JIA) is an inflammatory disease associated with bone loss and low bone mineral density (BMD). The treatment involves disease-modifying antirheumatic drugs, glucocorticoids (GCs) and biological agents. The aim of this study was to evaluate effects of 12-month therapy with the anti-tumor necrosis factor alpha (anti-TNFα) preparations on bone mineral density (BMD) and biochemical turnover markers (BTM) in adult patients with JIA who were previously either treated or not treated with glucocorticoids (GC) and to assess effects of the discontinuation of GCs on their bone status. Nineteen adult patients (12 women, 7 men) aged 18-33 years with active JIA were prospectively enrolled to receive the anti-TNFα therapy (infliximab, etanercept or adalimumab). BMD and BTMs were determined at baseline and 1-year follow-up. The anti-TNFα therapy resulted in a significant reduction in disease activity score 28 (DAS28) and C-reactive protein (CRP) and a significant increase in BMD at the lumbar spine and total body and in serum N-terminal propeptide of type I procollagen (PINP, marker of bone formation). No significant changes in serum beta C-terminal telopeptide of type I collagen (ßCTX, marker of osteoclastic bone resorption) and osteocalcin (marker of bone remodeling) were found. A significant negative correlation was observed between the change in the DAS28, CRP and serum PINP. The change in serum PINP concentrations positively correlated with the change in lumbar spine BMD. A significant increase in serum PINP was observed only in patients discontinuing GCs during the anti-TNFα treatment. After the initiation of the anti-TNFα therapy in young adults with JIA, the increase in new bone formation can be explained by discontinuation of GCs administration as the patients with the largest reduction in DAS28 and CRP probably are the ones most likely to stop GC.

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.

Hip fracture incidence from 1981 to 2009 in the Czech Republic as a basis of the country-specific FRAX model.

The aim of this study was to calculate rates of hospitalization for hip fracture and the incidence of hip fractures in the Czech Republic over a period of 29 years. A second aim was to use the most recent data to populate a FRAX(®) model for the assessment of fracture probability in individual patients. Data on hospitalizations for hip fracture (1981-2009) and number of women and men with hip fractures (2000-2009) were obtained, and incidences were computed for the entire population ≥50 years of age. Incidence of hospitalization for hip fracture in the Czech population aged ≥50 years increased progressively by calendar year. Age-standardized incidence of hip fractures increased to 2004 but leveled off thereafter and decreased after 2005. Data for hip fracture risk in 2008 and 2009 and the death hazard were used to populate a Czech-specific FRAX model for the computation of 10-year fracture probability. The customized FRAX model, using the verified epidemiological data, will be used to identify patients at increased fracture risk.

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.

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.

A comparison of the acute effects of calcium and strontium ranelate on the serum marker of bone resorption.

BACKGROUND: To investigate the mechanism by which strontium ranelate (SrR) inhibits the bone resorption, this study compared the effects of SrR and calcium on parathyroid hormone (PTH) and the biochemical marker of bone resorption (serum type 1 collagen cross-linked C-telopeptide, ßCTX). METHODS: In 10 healthy young subjects, after overnight fasting, 1000 mg of elemental calcium and 2000 mg of SrR containing 600 mg Sr²âº were administered consecutively with a 1 week washout period. During the control period no drug was given. Fasting blood samples were drawn at baseline and throughout the next 5-h period. RESULTS: After the ingestion of either calcium or SrR, there was a significant increase in serum calcium and strontium concentrations, and a decrease in serum ßCTX and intact PTH concentrations as compared to the baseline values (p<0.05). In the fasting subjects, no significant differences in the variable were found as compared to the baseline values. CONCLUSIONS: The decrease in PTH and the marker of bone resorption observed after the SrR administration is comparable to the decrease observed after the calcium administration in young adults.

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.

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.

Geographical variation in DXA bone mineral density in young European men and women. Results from the Network in Europe on Male Osteoporosis (NEMO) study.

UNLABELLED: We collected population-based young normal hip and spine BMD data from 17 centres across Europe to assess between centre differences and to compare reference values with the US NHANES-III data. There was strong evidence of between country heterogeneity, but not between centres within countries. Hip BMD mean values were lower in European women, but SD's differed little from the NHANES-III USA results in both sexes. It may be necessary to adjust NHANES-III based T-scores by adding/subtracting a country-specific adjustment factor. INTRODUCTION: It remains unclear whether young normal BMD reference values specific to an American population can be validly used for T-score calculation in Europeans. METHODS: We collected population based BMD data from 1163 men and 329 women aged 19-29 years from 17 centres across Europe to compare mean and SD values with the NHANES-III study USA results. BMD(g/cm2) was measured at the hip and spine using DXA densitometers cross-calibrated with the European Spine Phantom (ESP). The only exclusions were for technically inadequate scans. A linear regression model was used to derive reference values. To allow for direct comparison with published NHANES III study data, the cross-calibrated BMD values were converted using the ESP equations to Hologic QDR 1000 units. RESULTS: In men, the overall mean(SD) BMD values expressed in Hologic-QDR1000 units of measurement, were: femoral neck 0.912(0.132); trochanter 0.793(0.124); and L2-L4 spine 1.027(0.123). The respective estimates in women were: 0.826(0.115); 0.670(0.093); and 0.983(0.107). However the I2 statistic for heterogeneity indicated moderate to strong evidence of between-centre heterogeneity. There was, however, no significant heterogeneity observed between centres within countries, suggesting that this variation arose from national differences. Compared to the NHANES III population-based US data, the mean values in women were significantly lower at both sites due to some lower national European means. However, at all sites and in both sexes the SD's were very similar between the US and Europe. There was some evidence that recruiting volunteers resulted in biased values in women. CONCLUSION: Our T-score normal values for the lumbar spine (L2-L4) should be more reliable for spine-specific risk assessment than some non-representative normal ranges, and should be evaluated for that purpose in Europe. If T-scores are to be used to compare individual data with ranges seen in normal young subjects of the same nationality, it may be necessary to adjust femoral NHANES III-based T-scores by adding (or subtracting) a country-specific adjustment factor. In risk assessment it is probably sufficient to use NHANES III-based hip T-scores, as supplied for the hip by densitometer manufacturers, interpreting them in light of recent international meta-analysis data on the relationship between BMD and fracture risk.