Race-specific FRAX models are evidence-based and support equitable care: a response to the ASBMR Task Force report on Clinical Algorithms for Fracture Risk.

Task Force on 'Clinical Algorithms for Fracture Risk' commissioned by the American Society for Bone and Mineral Research (ASBMR) Professional Practice Committee has recommended that FRAX® models in the US do not include adjustment for race and ethnicity. This position paper finds that an agnostic model would unfairly discriminate against the Black, Asian and Hispanic communities and recommends the retention of ethnic and race-specific FRAX models for the US, preferably with updated data on fracture and death hazards. In contrast, the use of intervention thresholds based on a fixed bone mineral density unfairly discriminates against the Black, Asian and Hispanic communities in the US. This position of the Working Group on Epidemiology and Quality of Life of the International Osteoporosis Foundation (IOF) is endorsed both by the IOF and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

[Actual treatment of osteoporosis].

Basing on European, American and Polish recommendation reviewed are strategy of treatment of osteoporosis. In Poland, rules of reimbursement reinforced general use of antiresorbtive drugs (bisphosponates, demosumab) in the treatment of osteoporosis. For effective therapy the key points are keeping the patient in the treatment and treatment monitoring with potential use of densitometry and bone markers.

Low dairy calcium intake is associated with overweight and elevated blood pressure in Polish adults, notably in premenopausal women.

OBJECTIVE: Dietary Ca is now being recognized to play an important role not only in skeletal integrity, but also in the regulation of energy and metabolism. The aim of the present study was to estimate the relationship of dairy Ca intake with BMI and blood pressure (BP) in a sample derived from the Polish population. DESIGN: Ca intake was calculated from an interviewer-administered semi-quantitative FFQ. BMI was calculated from measured weight and height, and BP was measured by a physician. SETTING: Cross-sectional epidemiological study on osteoporosis risk factors in Poland. SUBJECTS: Randomly selected healthy adult persons (n 1259; 750 women and 509 men). RESULTS: Dairy Ca intake was significantly lower in individuals with overweight/obesity (BMI≥25·00 kg/m2) and/or with elevated BP (systolic/diastolic ≥140/≥90 mmHg) than in those with normal body mass and BP, respectively. Ca intake was negatively correlated with BMI (r=-0·12, P<0·001), systolic BP (r=-0·11, P<0·001) and diastolic BP (r=-0·08, P<0·01). Daily dairy Ca intake below 1000 mg was a predictor for BMI≥25·0 kg/m2 (OR=1·44, P<0·005). This relationship was stronger in women, particularly premenopausal women. CONCLUSIONS: The obtained results indicate the role of low dairy Ca intake in the development of obesity and hypertension, notably in premenopausal women.

A genome-wide copy number association study of osteoporotic fractures points to the 6p25.1 locus.

BACKGROUND: Osteoporosis is a systemic skeletal disease characterised by reduced bone mineral density and increased susceptibility to fracture; these traits are highly heritable. Both common and rare copy number variants (CNVs) potentially affect the function of genes and may influence disease risk. AIM: To identify CNVs associated with osteoporotic bone fracture risk. METHOD: We performed a genome-wide CNV association study in 5178 individuals from a prospective cohort in the Netherlands, including 809 osteoporotic fracture cases, and performed in silico lookups and de novo genotyping to replicate in several independent studies. RESULTS: A rare (population prevalence 0.14%, 95% CI 0.03% to 0.24%) 210 kb deletion located on chromosome 6p25.1 was associated with the risk of fracture (OR 32.58, 95% CI 3.95 to 1488.89; p = 8.69 × 10(-5)). We performed an in silico meta-analysis in four studies with CNV microarray data and the association with fracture risk was replicated (OR 3.11, 95% CI 1.01 to 8.22; p = 0.02). The prevalence of this deletion showed geographic diversity, being absent in additional samples from Australia, Canada, Poland, Iceland, Denmark, and Sweden, but present in the Netherlands (0.34%), Spain (0.33%), USA (0.23%), England (0.15%), Scotland (0.10%), and Ireland (0.06%), with insufficient evidence for association with fracture risk. CONCLUSIONS: These results suggest that deletions in the 6p25.1 locus may predispose to higher risk of fracture in a subset of populations of European origin; larger and geographically restricted studies will be needed to confirm this regional association. This is a first step towards the evaluation of the role of rare CNVs in osteoporosis.

Risedronate in children with osteogenesis imperfecta: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Children with osteogenesis imperfecta are often treated with intravenous bisphosphonates. We aimed to assess the safety and efficacy of risedronate, an orally administered third-generation bisphosphonate, in children with the disease. METHODS: In this multicentre, randomised, parallel, double-blind, placebo-controlled trial, children aged 4-15 years with osteogenesis imperfecta and increased fracture risk were randomly assigned by telephone randomisation system in a 2:1 ratio to receive either daily risedronate (2·5 or 5 mg) or placebo for 1 year. Study treatment was masked from patients, investigators, and study centre personnel. Thereafter, all children received risedronate for 2 additional years in an open-label extension. The primary efficacy endpoint was percentage change in lumbar spine areal bone mineral density (BMD) at 1 year. The primary efficacy analysis was done by ANCOVA, with treatment, age group, and pooled centre as fixed effects, and baseline as covariate. Analyses were based on the intention-to-treat population, which included all patients who were randomly assigned and took at least one dose of assigned study treatment. The trial is registered with ClinicalTrials.gov, number NCT00106028. FINDINGS: Of 147 patients, 97 were randomly assigned to the risedronate group and 50 to the placebo group. Three patients from the risedronate group and one from the placebo group did not receive study treatment, leaving 94 and 49 in the intention-to-treat population, respectively. The mean increase in lumbar spine areal BMD after 1 year was 16·3% in the risedronate group and 7·6% in the placebo group (difference 8·7%, 95% CI 5·7-11·7; p<0·0001). After 1 year, clinical fractures had occurred in 29 (31%) of 94 patients in the risedronate group and 24 (49%) of 49 patients in the placebo group (p=0·0446). During years 2 and 3 (open-label phase), clinical fractures were reported in 46 (53%) of 87 patients in the group that had received risedronate since the start of the study, and 32 (65%) of 49 patients in the group that had been given placebo during the first year. Adverse event profiles were otherwise similar between the two groups, including frequencies of reported upper-gastrointestinal and selected musculoskeletal adverse events. INTERPRETATION: Oral risedronate increased areal BMD and reduced the risk of first and recurrent clinical fractures in children with osteogenesis imperfecta, and the drug was generally well tolerated. Risedronate should be regarded as a treatment option for children with osteogenesis imperfecta. FUNDING: Alliance for Better Bone Health (Warner Chilcott and Sanofi).

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.

Guidelines for the diagnosis and management of osteoporosis in Poland. Update 2022.

Guidelines to provide an update of the previously published Polish recommendations for the management of women and men with osteoporosis have been developed in line with advances in medical knowledge, evidence-based data, and new concepts in diagnostic and therapeutic strategies. A Working Group of experts from the Multidisciplinary Osteoporosis Forum and from the National Institute of Geriatrics, Rheumatology, and Rehabilitation in Warsaw performed a thorough comprehensive review of current relevant publications in the field (including all age groups of people and management of secondary osteoporosis), and they evaluated epidemiological data on osteoporosis in Poland and the existing standards of care and costs. A voting panel of all co-authors assessed and discussed the quality of evidence to formulate 29 specific recommendations and voted independently the strength of each recommendation. This updated practice guidance highlights a new algorithm of the diagnostic and therapeutic procedures for individuals at high and very high fracture risk and presents a spectrum of general management and the use of medication including anabolic therapy. Furthermore, the paper discusses the strategy of primary and secondary fracture prevention, detection of fragility fractures in the population, and points to vital elements for improving management of osteoporosis in Poland.

Bone metabolism in cholestatic children before and after living-related liver transplantation--a long-term prospective study.

Bone disorders are common in children with end-stage liver diseases, especially those associated with cholestasis. Abnormal hepatocyte function, disordered vitamin D metabolism and calcium-phosphorous homeostasis, malnutrition, and immunosuppressive treatment are potential risk factors of bone tissue pathology before and after transplantation. The aim of the study was to analyze the long-term effect of successful living-related liver transplantation (LRLTx) on skeletal status and bone metabolism in cholestatic children. Eighteen cholestatic children (1.4±0.5yr old; 12 females [F]/6 males [M]) qualified for LRLTx were analyzed; 16 (5F/11M) of them participated in long-term observation (V4). Serum levels of osteocalcin (OC), procollagen type 1 N-terminal propeptide (P1NP), cross-linked telopeptide of type 1 collagen (CTx), insulin-like growth factor I (IGF-I), IGF-I binding protein 3 (IGFBP-3), parathyroid hormone (PTH), 25-hydroxyvitamin D (25(OH)D), and 1,25-dihydroxyvitamin D (1,25(OH)(2)D) were assayed before (V0) and 6mo (V1), 12mo (V2), 18mo (V3), and 4.4yr (V4) after LRLTx. Total body bone mineral content (TBBMC) and total body bone mineral density (TBBMD) were measured by dual-energy X-ray absorptiometry (DXA) at the same pattern. Before LRLTx, the OC, P1NP, CTx, IGF-I, and IGFBP-3 levels as well as TBBMC and TBBMD were decreased compared with age-matched control group. The mean serum levels of 25(OH)D and 1,25(OH)(2)D were within reference ranges from V0 to V4. After LRLTx, the OC, P1NP, CTx, IGF-I, and IGFBP-3 as well as TBBMC and TBBMD reached the age-matched reference values. At V4, the level of P1NP decreased below and the PTH increased above the reference range that coincided with reduced Z-scores of both TBBMC (-1.11±1.24) and TBBMD (-1.00±1.19). P1NP and CTx, both measured at V3, correlated with IGF-I at V2 (R=0.86, p=0.014 and R=0.78, p=0.021, respectively) and PTH at V3 for P1NP and V1 for CTx (R=0.64, p=0.048 and R=0.54, p=0.038, respectively). The TBBMC changes between V0 and V4 correlated with IGF-I (R=0.68, p=0.015) and 1,25(OH)(2)D (R=0.54, p=0.025), both assayed at V1. The change of TBBMC Z-scores between V0 and V4 correlated with P1NP at V1 (R=0.69, p=0.002). The TBBMD changes between V0 and V4 correlated with CTx at V1 (R=0.54, p=0.027) and P1NP change between V0 and V1 (R=0.51, p=0.038). In short-term observation, successful LRLTx led to bone metabolism normalization triggered by probable anabolic action of IGF-I and PTH and manifested by TBBMC and TBBMD increases. In long-term horizon, moderately impaired DXA assessed bone status coincided with disturbances in bone metabolism. Bone metabolism markers, especially P1NP and CTx, appeared to be good predictors of changes in bone status evaluated by DXA.

Skeletal status and body composition in young women with functional hypothalamic amenorrhea.

CONTEXT: Functional hypothalamic amenorrhea (FHA) related to hypoestrogenism and hormonal status may influence skeletal homeostasis and body composition. The study aimed to evaluate hormones concentrations, body composition and bone strength in FHA cases. PATIENTS AND METHODS: Total body scans using DXA method (DPX-L, GE Lunar) were performed in a group of 27 women aged 21.8 years ± 3.9 with FHA related to weight loss. References of healthy control subjects were used to calculate Z-scores (age and gender matched), SD-scores (height and gender matched), and SDs-scores (weight and gender matched). Whole skeleton bone mineral content (TBBMC, g) and density (TBBMD, g/cm(2)), lumbar spine (L2-L4) bone mineral density (SBMD; g/cm(2)), lean body mass (LBM, g) and fat mass (FM, g) were investigated. Relative bone strength index was calculated as the TBBMC/LBM ratio. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, testosterone, and prolactin (PRL) concentrations were assayed to characterize hormonal profile of FHA cases. RESULTS: Hormonal evaluation in patients with FHA revealed significantly decreased serum concentrations of gonadotropins and estradiol. Serum LH concentrations were 1.47 ± 0.89 mIU/ml, FSH 4.44 ± 1.94 mIU/ml. Estradiol concentrations in serum were 27.08 ± 13.10 pg/ml. As evidenced by Z-scores, FHA cases had decreased SBMD, TBBMD and TBBMC Z-scores of -1.23 ± 0.90 (p < 0.0001), -0.72 ± 0.86 (p < 0.001), and -0.90 ± 1.40 (p < 0.01), respectively. Reduced FM, LBM and FM/LBM ratio Z-scores of -1.80 ± 2.28 (p < 0.001), -0.59 ± 1.49 (p < 0.05) and -0.74 ± 1.55 (p < 0.05), but not TBBMC/LBM Z-score of -0.54 ± 2.14 (ns) were noted in FHA cases compared with healthy control cases. TBBMC, TBBMD, TBBMC/LBM when BH- or BW-matched were normal as evidenced by SD-scores and SDs-scores. SBMD remained reduced when BH-matched (SD-score = -0.40 ± 0.86; p < 0.05) whereas FM and FM/LBM were lower than expected in healthy, both compared to BH- and BW-dependent references. The length of amenorrhea in months negatively correlated with SBMD Z-score (R = -0.39, p < 0.05), and SD-scores for SBMD (R = -0.48), TBBMD (R = -0.43), TBBMC (R = -0.46) (all p < 0.05) and positively with SDs-scores for FM (R = 0.44, p < 0.05). CONCLUSION: Patients with FHA were characterized by lower concentrations of serum FSH, LH and estradiol concentrations. Moreover, FHA cases had decreased FM and an imbalanced relationship between BW, FM, and LBM. Despite reduced BMD and BMC, bone strength was not significantly affected by FHA.

[Pathologies of calcium-phosphate homeostasis]. / Patologie zwiazane z gospodarka wapniowo-fosforanowa.

The colossal progress in understanding of vitamin D and phosphate metabolism introduces new perspectives in chronic kidney disease (CKD) therapy. Increasing demand for phosphate excretion per nephron triggers the vicious cycle that leads to increase in FGF-23 and PTH and decrease in vitamin D and Klotho. Restriction of dietary phosphate intake (low phosphate diet) and administration of phosphate binder can be regarded as the most important interventions in this case. Because the vicious cycle is likely activated long before hyperphosphatemia occurs during CKD progression, phosphate restriction would have been more effective if started before serum phosphate levels increased, perhaps as soon as serum FGF-23 levels rose. Phosphate restriction alleviates phosphate overload per nephron and can disrupt the vicious cycle: phosphate restriction can reduce serum FGF-23 levels and increase vitamin D, which in turn increase Klotho expression in kidney and parathyroid glands. Inhibitors of rennin-angiotensin system (rosiglitazone, angiotensin-converting enzyme inhibitors) and proper vitamin D supplementation may also up-regulate Klotho expression. Increased Klotho in the kidney may improve FGF-23 sensitivity, which further reduce the amount of FGF-23 required for excreting a given amount of phosphate. Increased Klotho in parathyroid may improve the ability of FGF-23 to suppress PTH. Proper supplementation with vitamin D increase the concentration of substrate for local 1,25(OH)2D synthesis 25(OH)D, which directly suppress PTH, increase Klotho, and decrease FGF-23 by proanabolic action on bone. Improving vitamin D status by inhibition of CYP24A is also under evaluation, as well as antibodies against FGF-23, as modern therapies in CKD.

Vitamin D supplementation and status in infants: a prospective cohort observational study.

OBJECTIVE: Vitamin D status in infants depends on supplementation. We examined the vitamin D status in relation to supplementation dose and scheme in infants. PATIENTS AND METHODS: One hundred thirty-four infants age 6 months and 98 infants age 12 months (drop out 27%) were investigated. Vitamin D intake (diet, supplements), anthropometry, and 25-hydroxyvitamin D (25-OHD) serum concentration at the 6th and 12th months were assessed. RESULTS: Vitamin D intake of 1062 ± 694 IU at the 6th month was not different from that at the 12th month (937 ± 618 IU). Vitamin D intake expressed in international units per kilogram of body weight decreased from 141 ± 80 IU/kg at the 6th month to 93 ± 62 IU/kg at the 12th month (P < 0.0001), which was associated with a reduction in 25-OHD from 43 ± 20 ng/mL to 29 ± 12 ng/mL, respectively (P < 0.0001). In the subgroup of everyday supplemented infants (n = 43), vitamin D intake decreased from 143 ± 88 IU/kg at the 6th month to 118 ± 60 IU/kg at the 12th month (P < 0.05), which coincided with a reduction of 25-OHD from 40 ± 19 ng/mL to 32 ± 13 ng/mL (P < 0.01). In the subgroup with variable supplementation habits (n = 32), vitamin D intake decreased from 146 ± 79 IU/kg to 77 ± 56 IU/kg (P < 0.001), which was associated with a reduction of 25-OHD from 42 ± 21 ng/mL to 25 ± 8 ng/mL (P < 0.0001). 25-OHD concentration change between the 6th and the 12th months negatively correlated with the 25-OHD level assessed at the 6th month (r = -0.82; P < 0.0001). CONCLUSIONS: Vitamin D supplementation of infants should consider their rapid body weight increment. We postulate vitamin D daily dose close to 100 IU/kg body weight as favorable for infants up to age 12 months.

Official Positions for FRAX® Bone Mineral Density and FRAX® simplification from Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX®.

Tools to predict fracture risk are useful for selecting patients for pharmacological therapy in order to reduce fracture risk and redirect limited healthcare resources to those who are most likely to benefit. FRAX® is a World Health Organization fracture risk assessment algorithm for estimating the 10-year probability of hip fracture and major osteoporotic fracture. Effective application of FRAX® in clinical practice requires a thorough understanding of its limitations as well as its utility. For some patients, FRAX® may underestimate or overestimate fracture risk. In order to address some of the common issues encountered with the use of FRAX® for individual patients, the International Society for Clinical Densitometry (ISCD) and International Osteoporosis Foundation (IOF) assigned task forces to review the medical evidence and make recommendations for optimal use of FRAX® in clinical practice. Among the issues addressed were the use of bone mineral density (BMD) measurements at skeletal sites other than the femoral neck, the use of technologies other than dual-energy X-ray absorptiometry, the use of FRAX® without BMD input, the use of FRAX® to monitor treatment, and the addition of the rate of bone loss as a clinical risk factor for FRAX®. The evidence and recommendations were presented to a panel of experts at the Joint ISCD-IOF FRAX® Position Development Conference, resulting in the development of Joint ISCD-IOF Official Positions addressing FRAX®-related issues.

beta-Carotene deficiency in cholestatic liver disease of childhood is caused by beta-carotene malabsorption.

BACKGROUND: : Depletion of beta-carotene (b-c) has not been extensively studied in children with chronic cholestatic liver disease. PATIENTS AND METHODS: : We assessed b-c serum concentration in 53 children with cholestatic liver disease: 19 patients operated on for biliary atresia, 12 with Alagille syndrome, and 22 with progressive familial intrahepatic cholestasis. To test b-c absorption, 6 children with chronic cholestasis received a load of 10 mg b-c/kg body weight. RESULTS: : We found decreased b-c concentrations in 45 patients. The absorption of b-c was not detectable in 5 of 6 children studied. CONCLUSIONS: : b-c depletion is a common problem of chronic cholestatic liver disease in childhood that can be attributed to disturbed intestinal absorption.

The evaluation of consistency between body composition assessments in pediatric population using pencil beam and fan beam dual-energy x-ray absorptiometers.

The replacement of the old dual-energy X-ray absorptiometry system with a novel one should be preceded by a cross-calibration procedure. Therefore, the study was aimed at investigating the consistency of bone and body composition measures performed in pediatric population using pencil beam (DPX-L; GE Healthcare, GE Healthcare, Madison, WI) and fan beam (Prodigy; GE Healthcare, GE Healthcare, Madison, WI) densitometers. The study group consisted of 212 healthy children aged 4-18yr. Total body (TB) and lumbar spine (S) (L2-L4) measurements were performed using DPX-L and Prodigy during the same visit. Bland-Altman analysis, linear regressions, and paired t-test were performed to evaluate the consistency of measurements and to establish a cross-calibration equation. The average Prodigy values for TB and lumbar spine bone mineral density (BMD) and content (BMC) were 2.7%, 2.4% and 1.6%, 1.6% higher than those of DPX-L, respectively (p<0.0001). Prodigy-assessed bone area (BA) was lower by 1.4% for TBBA (p<0.0001) and 1.1% for SBA (p<0.001). Lean body mass (LBM) from Prodigy was higher by 6.9% (p<0.0001), whereas fat mass (FM) was lower by 8.4% compared with those from DPX-L (p<0.0001). Bland-Altman analyses revealed the effect of magnitude that was nonlinear (2nd degree polynomial) for TBBMD (r=0.32, p=0.001), TBBMC (r=0.51, p<0.0001), TBBA (r=0.34, p<0.0001), and LBM (r=0.56, p<0.0001), but not for FM (r=0.14, not significant [n.s.]). In contrast, in lumbar spine, the magnitude dependence was linear and significant for SBMC (r=0.46, p<0.0001) and SBA (r=0.34, p<0.0001) but not for SBMD (r=0.12, n.s.). Both skeletal and body composition variables assessed by DPX-L and Prodigy devices were highly correlated, showing R(2) values ranging from 0.976 for FM to 0.994 for SBMC. The results of this study document a necessity for implementation of calculated cross-calibration equations to transform DPX-L-based local pediatric references into a novel Prodigy system.

[Prophylaxis of vitamin D deficiency--Polish recommendation 2009]. / Stanowisko Zespolu Ekspertów. Polskie zalecenia dotyczace profilaktyki niedoborów witaminy D - 2009.

Adequate vitamin D intake and its status are important not only for bone health and Ca-P metabolism, but for optimal function of many organs and tissues throughout the body. Due to documented changes in dietary habits and physical activity level, both observed in growing children and adults, the prevalence of vitamin D insufficiency is continuously increasing. Basing on current literature review and opinions of National Consultants and experts in the field, polish recommendations for prophylactic vitamin D supplementation in infants, toddlers, children and adolescents as well as in adults, including pregnant and lactating women have been established.

[Prophylaxis of vitamin D deficiency--Polish recommendations 2009]. / Polskie zalecenia dotyczace profilaktyki niedoborów witaminy D--2009.

Appropriate state procurement system for vitamin D is important not only for the proper functioning of the skeletal, maintaining calcium and phosphorus homeostasis, but also for a number of other organs and tissues in our body. In connection with the change in lifestyle including dietary habits change, the widespread use of UV filters and less outdoor activity, observed an increase in the percentage of vitamin D deficiency, both in population and developmental age and adults. Based on the results of recent scientific research team of experts provides recommendations for preventive Polish supply of vitamin D in infants, children, adolescents and adults, including pregnant women and nursing mothers.

[Mechanisms of action of anticatabolic drugs used in osteoporosis therapy]. / Mechanizmy dzialania leków antykatabolicznych stosowanych w osteoporozie.

Bone remodeling is essential for skeletal and the whole body health. Imbalance in skeletal turnover, so that bone resorption exceeds bone formation, may lead to reduction in bone strength and increase fractures risk. The main target of anticatabolic therapy is to normalize increased osteoclasts activity and bone turnover. Molecular mechanisms of action of this class of drugs are related with different points in cellular signaling pathways that control osteoclasts differentiation and resorbing activity. These mechanisms are briefly described in our review.

[Klotho - a new regulator of mineral homeostasis]. / Kloto - nowy regulator gospodarki mineralnej.

Research on the regulation of mineral homeostasis have been continuing for the decades, with an effect of establishing the impression that the governing mechanisms are already fairly well known and understood. Revealing of the molecular mechanism of action of the Klotho protein, forced us to revise this knowledge. It is known already that Kloto is a unique regulatory efector playing key role in reversing the imbalanced extracellular Ca(++) concentrations, by affecting the intensity of the transepithelial transport and modulation of the parathormone excretion. In cooperation with the phosphaturic hormone - Fgf23 it regulates calcium concentration by suppression of 1,25(OH)(2)D synthesis, and reabsorption of phosphate in a distal convoluted part of nephron. Acting through these mechanisms Klotho takes part in the regulation of the mineral homeostasis of cerebrospinal fluid, blood and body fluids acting on the choroid plexus, parathyroid glands and distal convoluted nephrons. In that way Klotho becomes one of the main players in a complex and multilevel system of maintaining the mineral homeostasis of the organism.

Critical points in strategies for the diagnosis and treatment of osteoporosis.

Current treatment decisions for osteoporosis depend on the fracture risk calculated based on the results of comprehensive diagnostic procedures [clinical risk factors (CRF), densitometry (BMD), morphometry, and bone turnover markers (BTM)]. Recently developed fracture risk assessment tool (FRAX) represents an important new achievement as a 10-year fracture risk calculation based on femoral neck densitometry and age combined with independent clinical fracture risk factors. FRAX presents several options: FRAX BMI (body mass index) is advocated as a helpful screening tool to identify the group of patients with high fracture risk, independently of access to densitometry and FRAX, utilizing hip densitometry. In both cases, the probability of major fractures or hip fractures are calculated during performed diagnostic evaluations. Operating FRAX algorithm does not include spinal bone mineral density, which is its main limitation. With the aim of improvement of anti-fracture efficacy of therapeutic management of osteoporosis, we have extended our discussion to three integral elements of existent strategy: 1) screening outlines, 2) principles of drug selection, and 3) treatment benefit evaluation. Since osteoporosis is a chronic disease, long-term adherence to the treatment is important. The suitability of the drug, the patient's preference, tolerability, and convenience should all be considered. Anti-catabolic drugs are most appropriate in patients with high bone turnover, while anabolic drugs demonstrate efficacy irrespective of bone turnover. BMD measurement is most widely used for long-term assessment of the efficacy of osteoporosis treatment. The measurements of bone turnover markers (BTMs) can be considered a useful shortterm (at 3 months) monitoring tool in selected patients. In both BTM and BMD, the least significant change (LSC) method should be used for interpretation of the results. Fractures are not a reliable clinical endpoint for evaluating the effectiveness of therapy in individual patients because of their stochastic nature. If fractures occur, however, the need for drug change and additional non-pharmacological treatment (fall prevention, balance training, muscle strengthening) should always be considered.

Identification of vertebral deformities in the Polish population by morphometric X-ray absorptiometry - results of the EPOLOS study.

INTRODUCTION: The aim of the study was the determination of the prevalence of asymptomatic vertebral deformities in healthy persons of the Polish population, based on morphometric X-ray absorptiometry (MXA), and comparison of the results with data from literature, obtained by other techniques. MATERIAL AND METHODS: The study involved 829 persons, including 520 women and 309 men, aged 18-79 years, untreated for osteoporosis before. The Th(4) to L(4) vertebrae were examined. Lateral scans of the thoracic-lumbar spine were made by an Expert-XL densitometer. Six point digitization was used to calculate the anterior (Ha), central (Hc), and posterior (Hp) height of the Th(4)-L(4) vertebral bodies. The vertebrae were defined as having prevalent deformities when at least one ratio value (Ha/Hp, Hc/Hp, Hp/Hp up, or Hp/Hp low) fell 3 SDs below or even more than the reference mean of that ratio at any vertebral level. RESULTS: The analysis was performed on 9629 vertebrae, of which 167 (1.75%), evaluated as deformed and considered as fractures, were observed in 113 patients (13.63 % of the examined patients). In 81 persons (74% of the patients with fractures; 9.7% of the studied population), single fractures were demonstrated, while in 28 persons, multiple deformities prevailed. Fractures occurred in 108 women (20.7% of the examined women) and 42 men (13.5% of the examined men). The highest incidence of deformities was observed in women over 55 years of age. First-degree deformities dominated. Deformities of the Th(8) and Th(6) vertebrae were most frequently observed. CONCLUSIONS: 1. Using MXA, it was found that in the Polish population deformities of vertebrae are common, as was demonstrated in X-ray morphometric studies in the European Vertebral Observation Study (EVOS). 2. Densitometric morphometry, as a non-invasive technique, may become a useful tool in the diagnostics of vertebral fractures.