Efficacy of teriparatide compared with risedronate on FRAX®-defined major osteoporotic fractures: results of the VERO clinical trial.

FRAX® calculates the 10-year probability of major osteoporotic fractures (MOF), which are considered to have a greater clinical impact than other fractures. Our results suggest that, in postmenopausal women with severe osteoporosis, those treated with teriparatide had a 60% lower risk of FRAX®-defined MOF compared with those treated with risedronate. INTRODUCTION: The VERO trial was an active-controlled fracture endpoint clinical trial that enrolled postmenopausal women with severe osteoporosis. After 24 months, a 52% reduction in the hazard ratio (HR) of clinical fractures was reported in patients randomized to teriparatide compared with risedronate. We examined fracture results restricted to FRAX®-defined major osteoporotic fractures (MOF), which include clinical vertebral, hip, humerus, and forearm fractures. METHODS: In total, 1360 postmenopausal women (mean age 72.1 years) were randomized to receive subcutaneous daily teriparatide (20 µg) or oral weekly risedronate (35 mg). Patient cumulative incidence of ≥ 1 FRAX®-defined MOF and of all clinical fractures were estimated by Kaplan-Meier analyses, and the comparison between treatments was based on the stratified log-rank test. Additionally, an extended Cox model was used to estimate HRs at different time points. Incidence fracture rates were estimated at each 6-month interval. RESULTS: After 24 months, 16 (2.6%) patients in the teriparatide group had ≥ 1 low trauma FRAX®-defined MOF compared with 40 patients (6.4%) in the risedronate group (HR 0.40; 95% CI 0.23-0.68; p = 0.001). Clinical vertebral and radius fractures were the most frequent FRAX®-defined MOF sites. The largest difference in incidence rates of both FRAX®-defined MOF and all clinical fractures between treatments occurred during the 6- to 12-month period. There was a statistically significant reduction in fractures between groups as early as 7 months for both categories of clinical fractures analyzed. CONCLUSION: In postmenopausal women with severe osteoporosis, treatment with teriparatide was more efficacious than risedronate, with a 60% lower risk of FRAX®-defined MOF during the 24-month treatment period. Fracture risk was statistically significantly reduced at 7 months of treatment. CLINICAL TRIAL INFORMATION: ClinicalTrials.gov Identifier: NCT01709110 EudraCT Number: 2012-000123-41.

Long-term denosumab treatment restores cortical bone loss and reduces fracture risk at the forearm and humerus: analyses from the FREEDOM Extension cross-over group.

Upper limb fractures (including wrist, forearm, and humerus) represent a significant burden among postmenopausal women with osteoporosis. Up to 7 years of treatment with denosumab resulted in an increase in bone mineral density and decrease in fractures in upper limb sites. INTRODUCTION: Upper limb (wrist, forearm, and humerus) fractures are a significant burden in osteoporosis, associated with significant morbidity and mortality. Denosumab, a monoclonal antibody against RANK ligand, increases bone mineral density (BMD) and decreases vertebral, nonvertebral, and hip fractures. Here, we evaluated the long-term effect of denosumab treatment on upper limb fracture risk and BMD. METHODS: In the FREEDOM trial, subjects were randomized 1:1 to receive every-6-month denosumab 60 mg or placebo subcutaneously for 3 years, after which all subjects could receive denosumab for up to 7 years (Extension). Among placebo subjects who completed FREEDOM and enrolled in the Extension, wrist, forearm, humerus, and upper limb fracture rates and rate ratios between different time periods (FREEDOM years 1-3, Extension years 1-3, and Extension years 4-7) were computed. BMD at the ultradistal radius, 1/3 radius, and total radius was analyzed in a subset of subjects in a BMD substudy. RESULTS: This analysis included 2207 subjects (116 in the BMD substudy). Fracture rates decreased over the 7-year Extension; fracture rate ratios between Extension years 4-7 (denosumab) and FREEDOM years 1-3 (placebo) reduced significantly for the wrist (0.57), forearm (0.57), humerus (0.42), and upper limb (0.52; p < 0.05 for all). Percentage increase in BMD from Extension baseline at the ultradistal radius, 1/3 radius, and total radius was significant by Extension year 7 (p < 0.05 for all). CONCLUSIONS: Long-term treatment with denosumab decreases upper limb fracture risk and increases forearm BMD, suggesting beneficial effects on both cortical and trabecular bone accruing over time.

Teriparatide treatment in a heart transplant patient with a chronic kidney disease and a low-turnover bone disease: a case report.

Low-turnover bone disease is a complication of chronic kidney disease and a long-term steroid therapy. Currently, the only bone anabolic treatment available is teriparatide (TPTD). So far, no data exist in heart transplant patients, and only one single case with histomorphometric analysis of a dialysis patient with a low-turnover bone disease has been published. The current report shows the effect of a 1-year TPTD therapy in a cardiac transplant patient with 10 vertebral and 3 peripheral fractures who had developed a chronic kidney failure while receiving triple immunosuppressive therapy. A transiliac bone biopsy following tetracycline labeling was performed prior and after 1 year of treatment, showing an increase in the bone formation and improvement of the structural indices (20-fold increase of osteoid volume/bone volume, fourfold increase of osteoid surface/bone surface and increases of wall thickness (+15%), trabecular thickness (+9%), and trabecular number (+38%)). Bone mineral density was stable, no new vertebral fractures had occurred, the therapy was well-tolerated, and the patient improved clinically.

Effect of vitamin D3 on bone turnover markers in critical illness: post hoc analysis from the VITdAL-ICU study.

In this post hoc analysis of the VITdAL-ICU study, an RCT in critically ill adults with 25-hydroxyvitamin D levels ≤20 ng/ml, vitamin D3 did not have a significant effect on ß-Crosslaps and osteocalcin. INTRODUCTION: Observational studies have shown accelerated bone loss in ICU survivors. A reversible contributor is vitamin D deficiency. In a post hoc analysis of the VITdAL-ICU study, we evaluated the effect of high-dose vitamin D3 on the bone turnover markers (BTM) ß-Crosslaps (CTX) and osteocalcin (OC). METHODS: The VITdAL-ICU study was a randomized, double-blind, placebo-controlled trial in critically ill adults with 25-hydroxyvitamin D levels ≤20 ng/ml who received placebo or high-dose vitamin D3 (a loading dose of 540,000 IU and starting 1 month after the loading dose five monthly maintenance doses of 90,000 IU). In this analysis on 289 survivors (209 telephone, 80 personal follow-up visits), BTM were analyzed on days 0, 3, 7, 28, and 180; self-reported falls and fractures were assessed. Bone mineral density (BMD) was measured after 6 months. RESULTS: At baseline, CTX was elevated; OC was low in both groups-after 6 months, both had returned to normal. There were no differences between groups concerning BTM, BMD, falls, or fractures. In linear mixed effects models, CTX and OC showed a significant change over time (p < 0.001, respectively), but there was no difference between the vitamin D and placebo group (p = 0.688 and p = 0.972, respectively). CONCLUSIONS: Vitamin D supplementation did not have a significant effect on BTM. Further studies should assess the effectiveness of vitamin D on musculoskeletal outcomes in ICU survivors.

Effects of vitamin D supplementation on glycated haemoglobin and fasting glucose levels in hypertensive patients: a randomized controlled trial.

AIM: To investigate the efficacy of vitamin D supplementation on glycaemic control. METHODS: The Styrian Vitamin D Hypertension Trial was a single-centre, double-blind, placebo-controlled study conducted between 2011 and 2014 at the Medical University of Graz, Austria. We enrolled 200 people with arterial hypertension and 25-hydroxyvitamin D [25(OH)D] concentrations <30 ng/mL. Study participants were randomized to receive either 2800 IU of vitamin D or placebo per day for 8 weeks. The present study was a post hoc analysis that incorporated an analysis of covariance (ancova) approach, while adjusting for baseline differences. RESULTS: A total of 185 participants [mean ± standard deviation age, 60.1 ± 11.3 years; 47% women; mean 25(OH)D 21.2 ± 5.6 ng/mL, mean glycated haemoglobin (HbA1c) 44.8 ± 11.8 mmol/mol and mean body mass index 30.4 ± 5.4 kg/m(2) ] completed the trial. ancova showed a mean treatment effect [95% confidence interval (CI)] on HbA1c of -3.52 (-6.7 to -0.34) mmol/mol (p = .045). There was no difference in fasting glucose -4.7 mg/dL (95% CI -16.3 to 6.9; p = .426). CONCLUSIONS: Vitamin D supplementation in obese hypertensive patients with low 25(OH)D reduces HbA1c levels. This finding warrants further investigation into potential vitamin D effects on glucose homeostasis.

Persistence, adherence, and medication-taking behavior in women with postmenopausal osteoporosis receiving denosumab in routine practice in Germany, Austria, Greece, and Belgium: 12-month results from a European non-interventional study.

UNLABELLED: Persistence with and adherence to osteoporosis therapy are critical for fracture reduction. This non-interventional study is evaluating medication-taking behavior of women with postmenopausal osteoporosis (PMO) receiving denosumab in Germany, Austria, Greece, and Belgium. Patients were representative of the PMO population and highly persistent with and adherent to denosumab at 12 months. INTRODUCTION: Persistence with and adherence to osteoporosis therapy are important for optimal treatment efficacy, namely fracture reduction. This ongoing, non-interventional study will evaluate medication-taking behavior of women with postmenopausal osteoporosis (PMO) receiving denosumab in routine practice in four European countries. METHODS: The study enrolled women who had been prescribed subcutaneous denosumab (60 mg every 6 months) in accordance with prescribing information and local guidelines. Persistence was defined as receiving the subsequent injection within 6 months + 8 weeks of the previous injection. Adherence was defined as receiving two consecutive injections within 6 months ± 4 weeks of each other. Medication coverage ratio (MCR) was calculated using the time a patient was covered with denosumab, as assessed from prescription records. Treatment was assigned prior to and independently of enrollment; outcomes are recorded during routine practice. RESULTS: These planned 12-month interim analyses included data from 1500 patients from 141 sites. Mean age was 66.4-72.4 years, mean baseline total hip T-scores ranged from -2.0 to -2.1 and femoral neck T-scores from -2.2 to -2.6, and 30.7-62.1% of patients had prior osteoporotic fracture. Persistence was 87.0-95.3%, adherence 82.7-89.3%, and MCR 91.3-95.4%. In a univariate analysis, increased age, decreased mobility, and increased distance to the clinic were associated with significantly decreased persistence; parental history of hip fracture was associated with significantly increased persistence. CONCLUSIONS: These data extend the real-world evidence regarding persistence with and adherence to denosumab, both of which are critical for favorable clinical outcomes, including fracture risk reduction.

Epidemiology of distal forearm fractures in Austria between 1989 and 2010.

UNLABELLED: Only few studies have been published hitherto on country-specific incidence of distal forearm fracture. In the prevailing study, incidences were estimated, and trend analyses were performed for the entire Austrian population aged ≥50á. Incidence decreased significantly in women, but not in men, over the past 12 years of observation. INTRODUCTION: To estimate incidence of distal forearm fracture and assess incidence trends in the entire Austrian population aged ≥50á from 1989-2010 for inpatient fractures and from 1999 to 2010 for all fractures. METHODS: The number of inpatient forearm fractures was obtained from the Austrian Hospital Discharge Register (AHDR) for the entire population aged ≥50á from 1989 to 2010. Total number of distal forearm fractures was modeled using patient-level data on 36,327 patients with distal forearm fractures. Crude and age-standardized incidence rates (cases per 100,000) were estimated in 5-year age intervals. To analyze the change in incidence over time, average annual changes expressed as incidence rate ratios (IRR) were calculated. RESULTS: For all distal forearm fractures, age-standardized incidence in women in 1999 and 2009 were estimated at 709 (95 % CI 675-743) and 607 (578-637), respectively. The age-standardized incidences in men the same years were estimated at 171 (156-185) and 162 (151-174), respectively. IRR analyses showed a significant decrease in women (-1.1 %, p < 0.01) but not in men (-0.8 %, p > 0.05) over the last 12 years (1999-2010). CONCLUSION: Incidence of distal forearm fracture in the entire Austrian population is comparable to hip fracture incidence which is known to be among the highest worldwide. However, trend analyses reveal a significant decrease for all distal forearm fractures in women, but not in men, over the last 12 years.

Epidemiology of proximal humeral fractures in Austria between 1989 and 2008.

UNLABELLED: Incidence rates of proximal humeral fractures in Austria over a period of twenty years (1989-2008) were estimated. Age standardized incidence rates increased until 2008, primarily driven by an increase in incidence rates in women. INTRODUCTION: The aim of the prevailing study was to estimate incidence rates of proximal humeral fractures and to assess changes in trend in the Austrian population aged 50 years and above, over a period of 20 years (1989-2008). METHODS: Number of proximal humeral fractures were obtained from the Austrian Hospital Discharge Register for the entire population >50 years of age. Adjustment factors were determined for multiple registrations of the same diagnosis, and for the fact that not all patients with proximal humeral fractures are treated in an inpatient setting. To analyze the overall change in this type of fracture for the period, average annual changes expressed as incidence rate ratios were calculated. RESULTS: The estimated age-standardized incidence (fractures per 100,000 individuals) of proximal humeral fractures among Austrians >50 years of age increased in men from 112 (95% CI, 99-124) to 141 (129-153) and in women from 222 (202-241) to 383 (360-406). The increase appeared to be linear with no leveling off towards the end of the study period. CONCLUSION: While some caution is necessary when interpreting the results given the use of adjustment factors, there appears to have been a rise in the incidence of proximal humeral fractures in Austria in both men and women, with no leveling off in recent years. The reasons for this are not clear, but in the light of previously reported leveling off in the increase in the incidence of hip fractures, a change in the patterns of falls cannot be ruled out.

Associations of homoarginine with bone metabolism and density, muscle strength and mortality: cross-sectional and prospective data from 506 female nursing home patients.

UNLABELLED: In female nursing home patients, homoarginine was associated with lower bone turnover, higher bone density, lower mortality and, by trend, with muscle strength. INTRODUCTION: Homoarginine, a cationic amino acid, may be relevant for muscusloskeletal health because it inhibits alkaline phosphatases (AP) and is involved in nitric oxide and energy metabolism. We aimed to evaluate whether homoarginine serum concentrations are associated with bone density and metabolism, muscle strength, fractures and mortality. METHODS: We examined a cohort of female nursing home patients that underwent quantitative bone ultrasound (QUS) measurements and assessments of knee extensor strength. Measurements of serum homoarginine, C-terminal telopeptide cross-links (ß-CTxs) and osteocalcin were also performed at baseline. Thereafter, patients were followed-up with respect to fractures and mortality. RESULTS: Serum homoarginine concentrations were determined in 506 female study participants (mean age: 83.9 ± 6.0 years). Homoarginine was inversely correlated with ß-CTxs (r = -0.26; p < 0.001) and osteocalcin (r = -0.21; p < 0.001), and these associations remained significant in multiple regression analyses. Multivariate regression analyses showed that homoarginine is significantly associated with calcaneus stiffness (beta coefficient = 0.11; p = 0.020) and by trend with knee extensor strength (beta coefficient = 0.09; p = 0.065). During a mean follow-up time of 27 ± 8 months, we recorded 119 deaths (23.5%) and 63 fractures (12.5%). In multivariate analyses, homoarginine was associated with significantly reduced risk of mortality and the combined endpoint of fractures and mortality. CONCLUSIONS: Whether homoarginine metabolism is critically involved into the pathogenesis of musculoskeletal diseases and fatal events warrants further studies.

How long should women with postmenopausal osteoporosis be treated with a bisphosphonate?

Bisphosphonates are very frequently prescribed to women suffering from postmenopausal osteoporosis with or without fragility fractures. The present review was aimed to update the available information on the most efficient treatment duration. Studies on bisphosphonate treatment duration were identified by Medline up to January 2013. Bisphosphonates are very effective in the short as well as in the medium-term. However, the optimal duration of use has not been determined yet. Therefore, this review summarizes the long-term effects of bisphosphonates on surrogate parameters of fracture prevention, bone mineral density measurements, and bone turnover markers. An initial treatment period of 3-5 years is recommended. Then, the patient has to be re-evaluated for fracture risk, which depends on fracture status as well as on other health issues. Beyond that, life style factors such as regular physical activity as well as a sufficient intake of calcium and vitamin D or, if necessary supplementation of calcium and/or vitamin D play an essential part in fracture prevention.

Low bone turnover and increase of bone mineral density in a premenopausal woman with postoperative hypoparathyroidism and thyroxine suppressive therapy.

We report the case of a 36-year-old woman who developed permanent hypoparathyroidism after thyroidectomy for differentiated thyroid carcinoma. A 6-year follow-up showed an increase of 11% in absolute bone mineral density at the spine and 6% at the hip accompanied by low bone turnover despite thyroid-stimulating hormone suppressive thyroxine therapy.

Epidemiology of hip fractures in Austria: evidence for a change in the secular trend.

UNLABELLED: Hip fracture incidence rates in Austria over a period of 20 years (1989-2008) were assessed. Age-standardized incidence rates increased until 2005 but decreased thereafter. This change in the secular trend was primarily driven by a decrease in hip fracture incidence in women. INTRODUCTION: The aim of the prevailing study was to assess the incidence rates of hip fractures including changes in trend in the Austrian population over a period of 20 years (1989-2008). METHODS: The number of hip fractures was obtained from the Austrian Hospital Discharge Register for the entire population ≥ 50 years of age. A correction factor for multiple registrations of the same diagnosis was determined. Incidence rates (cases per 100,000) of hip fracture were calculated in 5-year age intervals. To analyze the overall change in hip fracture for the period, average annual change expressed as incidence rate ratios (IRRs) was calculated. RESULTS: The age-standardized incidence in women increased until 2005, from 493 to 642, and decreased thereafter. In men, it increased at a measured pace until 2006, from 192 to 280, and decreased thereafter with a slight rebound in 2008. The age-standardized incidence in the entire population increased until 2005, from 376 to 496, and decreased thereafter. The IRR for the last 3 years (2006-2008) was significantly below the IRR for the first 17 years (0.94, ρ < 0.01), driven by a lower IRR in women (0.91, ρ < 0.01) and to a lesser extent by a lower IRR (not statistically significant) in men (0.96, ρ < 0.15). CONCLUSION: The present study indicates that since 2006, age-standardized incidence of hip fractures has been declining in the Austrian population aged 50 years and above. This reversal in the secular trend has primarily been driven by a decrease in hip fracture incidence in women.

Fracture rate and back pain during and after discontinuation of teriparatide: 36-month data from the European Forsteo Observational Study (EFOS).

UNLABELLED: In this observational study in postmenopausal women with severe osteoporosis, the incidence of fractures was decreased during 18 months of teriparatide treatment with no evidence of further change in the subsequent 18-month post-teriparatide period when most patients took other osteoporosis medications. Fracture reduction was accompanied by reductions in back pain. INTRODUCTION: To describe fracture outcomes and back pain in postmenopausal women with severe osteoporosis during 18 months of teriparatide treatment and 18 months post-teriparatide in normal clinical practice. METHODS: The European Forsteo Observational Study (EFOS) was a prospective, multinational, observational study. Data on incident clinical fractures and back pain (100 mm Visual Analogue Scale [VAS] and questionnaire) were collected. Fracture data were summarised in 6-month intervals and analysed using logistic regression with repeated measures. Changes from baseline in back pain VAS were analysed using a repeated measures model. RESULTS: A total of 208 (13.2%) of 1,576 patients sustained 258 fractures during 36 months of follow-up: 34% were clinical vertebral fractures and 66% non-vertebral fractures. The adjusted odds of fracture were reduced during teriparatide treatment and there was no evidence of further change in the 18-month post-teriparatide period, during which 63.3% patients took bisphosphonates. A 74% decrease in the adjusted odds of fracture in the 30- to <36-month period compared with the first 6-month period was observed (p < 0.001). Back pain decreased during teriparatide treatment and this decrease was sustained after teriparatide discontinuation. Adjusted mean back pain VAS decreased by 26.3 mm after 36 months (p < 0.001) from baseline mean of 57.8 mm. CONCLUSIONS: In a real-life clinical setting, the risk of fracture decreased during teriparatide treatment, with no evidence of further change after teriparatide was discontinued. The changes in back pain seen during treatment were maintained for at least 18 months after teriparatide discontinuation. These results should be interpreted in the context of the design of an observational study.

Serum albumin, subjective global assessment, body mass index and the bioimpedance analysis in the assessment of malnutrition in patients up to 15 years after liver transplantation.

BACKGROUND: The subjective global assessment (SGA) or the body mass index (BMI) is used to determine the nutritional state after LTX. Bioelectrical impedance analysis (BIA) is used as tool to determine body composition by nutritional care professionals. METHODS: BIA, SGA, BMI, and serum albumin (SA) levels were performed to assess malnutrition following liver transplantation. BIA measurement was used as reference standard to determine existing malnutrition. A phase angle (PA) <5 was used to define potentially existing chronic disease-related malnutrition as a standard. All other measured parameters were compared with respect to their prognostic accuracy regarding the prediction of malnutrition as compared to the mentioned standard. RESULTS: Seventy-one recipients (51 men, 20 women) were included. Median age was 58, weight 77 kg, BMI 26 kg/m(2) , PA 4.1°, and SA 4.3 g/dL. According to the Nutritional Risk Screening 2002, 9.4% (6/71), to BMI 15.4% (11/71), to SA 30.9% (22/71), and to BIA 36.5% (28/71) of the patients were malnourished. PA did not correlate with BMI or NA, there was a significant correlation with SA (p = 0.001). Univariate analysis revealed SA as independent predictor for malnutrition. ROC analysis for all parameters revealed a significantly (p < 0.05) better area under the receiver operating characteristic curve for SA (0.812) than for BMI (0.603) for the prediction of malnutrition. CONCLUSION: SGA or BMI calculation alone does not suffice to evaluate the nutritional status. SA seems to play a crucial role in the prediction of severe disease-related malnutrition in this special patient cohort.

Mind the gap: Incidence of osteoporosis treatment after an osteoporotic fracture - results of the Austrian branch of the International Costs and Utilities Related to Osteoporotic Fractures Study (ICUROS).

INTRODUCTION: Despite availability of effective treatment options proven to prevent osteoporotic fractures, a huge gap in osteoporosis treatment exists. The aim of the present study was to evaluate the treatment rate after a major osteoporotic fracture (MOF) in Austria, one of the 25 wealthiest countries worldwide. METHODS: This analysis is based on the data of the International Costs and Utilities Related to Osteoporotic Fractures Study (ICUROS), a prospective observational study assessing data from patients who suffered a MOF. We stratified these patients by treatment status at time of fracture and compared treatment use following MOF by sex as well as by fracture sites at the time of the index fracture, and 4, 12, and 18 months thereafter. Descriptive statistics, t-tests for continuous variables and chi-squared tests for nominal variables, were performed to compare treatment groups. RESULTS: A total of 915 patients (78 % female) were recruited at 8 different trauma centers throughout Austria. At the time of fracture, 731 patients (80 %) did not receive osteoporosis treatment. In this group, follow-up analysis after 4, 12 and 18 months revealed a treatment rate of 18 %, 16 %, 15 % in women, and 8 %, 12 %, 10 % in men, respectively. In those who received osteoporosis medication at the time of fracture the treatment rate was 65 %, 54 % and 60 % in women, and comparable results in men. CONCLUSIONS: Only 1 in 10 men, and less than 2 in 10 women of those who did not receive osteoporosis treatment at the time of fracture were prescribed an adequate osteoporosis treatment. Thus, the vast majority of patients who sustained an osteoporotic fracture and thus were at imminent risk of receiving subsequent fractures did not receive an adequate treatment. There is a clear need for the implementation of coordinated, multi-disciplinary models of care for secondary fracture prevention.

Histomorphometric changes by teriparatide in alendronate-pretreated women with osteoporosis.

SUMMARY: The level of increased bone formation after 24 months of treatment with teriparatide (rhPTH (1-34), TPTD) is similar in patients who were either treatment-naïve (TN) or had lower bone turnover initially due to previous alendronate (ALN) therapy. INTRODUCTION: Bone anabolic effects of TPTD in postmenopausal women with osteoporosis may be blunted during the initial phase after switching from ALN to TPTD. To explore the long-term implications, we examined histomorphometric and biochemical markers of bone turnover of patients on TPTD therapy after long-term ALN treatment. METHODS: Paired biopsies were obtained after tetracycline double labeling at baseline and after 24 months of TPTD treatment from 29 ALN-pretreated (64.5 ± 16.4 months) and 16 TN patients. Biochemical markers were measured at baseline, during the treatment, or at study end. RESULTS: Compared with the baseline, after 24-month TPTD, activation frequency (Ac.F.) and osteoid surface (OS) increased in both groups: 0.11-0.34 cycles per year, 3.96-9.8% in the ALN-pretreated group and 0.19-0.33 cycles per year, 6.2-11.3% (p < 0.05) in the TN group, respectively. Biochemical and histomorphometric markers correlated positively both at baseline and endpoint. Serum amino terminal propeptide of type I procollagen (PINP) correlated with Ac.F. (r = 0.57, p < 0.001 and r = 0.48, p < 0.01) and OS (r = 0.51, p < 0.01 and r = 0.56, p < 0.01) at baseline and endpoint, respectively. Following 3 months of treatment, increases in biochemical markers like PINP predicted the increase in Ac.F. (r = 0.52, p < 0.01) and OS (r = 0.54, p < 0.01) after 24 months. CONCLUSIONS: The increased level of formation is similar in patients who were either TN or had lower bone turnover initially due to previous ALN therapy. Elevated bone formation in postmenopausal women with osteoporosis was sustained over a 24-month period by TPTD. Biochemical markers of bone formation are a good surrogate for the assessment of TPTD effects.

Effects of a long-term vitamin D and calcium supplementation on falls and parameters of muscle function in community-dwelling older individuals.

UNLABELLED: In 242 community-dwelling seniors, supplementation with either 1000 mg of calcium or 1000 mg of calcium plus vitamin D resulted in a decrease in the number of subjects with first falls of 27% at month 12 and 39% at month 20. Additionally, parameters of muscle function improved significantly. INTRODUCTION: The efficacy of vitamin D and calcium supplementation on risk of falling in the elderly is discussed controversially. Randomized controlled trials using falls as primary outcome are needed. We investigated long-term effects of calcium and vitamin D on falls and parameters of muscle function in community-dwelling elderly women and men. METHODS: Our study population consisted of 242 individuals recruited by advertisements and mailing lists (mean [ +/- SD] age, 77 +/- 4 years). All serum 25-hydroxyvitamin D (25[OH]D) levels were below 78 nmol/l. Individuals received in a double blinded fashion either 1000 mg of calcium or 1000 mg of calcium plus 800 IU of vitamin D per day over a treatment period of 12 months, which was followed by a treatment-free but still blinded observation period of 8 months. Falls were documented using diaries. The study took place in Bad Pyrmont, Germany (latitude 52 degrees ) and Graz, Austria (latitude 46 degrees ). RESULTS: Compared to calcium mono, supplementation with calcium plus vitamin D resulted in a significant decrease in the number of subjects with first falls of 27% at month 12 (RR = 0.73; CI = 0.54-0.96) and 39% at month 20 (RR = 0.61; CI = 0.34-0.76). Concerning secondary endpoints, we observed significant improvements in quadriceps strength of 8%, a decrease in body sway of 28%, and a decrease in time needed to perform the TUG test of 11%. DISCUSSION: Combined calcium and vitamin D supplementation proved superior to calcium alone in reducing the number of falls and improving muscle function in community-dwelling older individuals.

The effect of RANKL and OPG on bone mineral density in pre-dialysis chronic renal failure.

AIMS: The influence of pre-dialysis chronic kidney disease (CKD) on bone is ill defined. Isolation of specific pathogenic mechanisms would improve the understanding and therapeutic options. We therefore investigated whether parathyroid dysfunction, altered vitamin D and hormonal status, or RANKL and OPG have an influence on bone mineral density (BMD) in patients with pre-dialysis renal failure. MATERIAL: 132 patients with chronic renal failure stage 1 - 5 (not yet on dialysis) were investigated in a cross sectional study. Osteoprotegerin (OPG), receptor activator of nuclear factor kB ligand (RANKL), parathyroid hormone (whole, intact and 7-84 fragment), bone markers, sex hormones, and vitamin D status were assessed together with femoral neck and trochanter z-score. Correlation and multivariate analyses were performed between the different parameters and BMD. RESULTS: In the multivariate analysis a significant association was found between the femoral neck z-score and sRANKL (B = -0.45; p < 0.001), and OPG (B = 0.20; p < 0.05). A significant negative association was also found between the trochanter z-score and sRANKL (B = -0.32; p < 0.001). No associations were found between the trochanter z-score and OPG or the sRANKL/OPG ratio. The body mass index was the only additional marker associated with both FN z-score (B = 0.20, p < 0.05) and TR z-score (B = 0.20, p < 0.05). Neither markers of osteoblast nor osteoclast activity, or intact PTH, whole PTH, the PTH 7-84 fragment or vitamin D status were related to bone mineral density. CONCLUSION: Our results demonstrate that the RANKL/RANK/OPG system is associated with bone mineral density in pre-dialysis chronic renal failure.

Calcium supply, bone mineral density and genetically defined lactose maldigestion in a cohort of elderly men.

OBJECTIVE: To examine a relationship of molecularly defined lactose malabsorption (LM; by LCT-polymorphism) to calcium supply, bone mineral density (BMD) and parameters of bone metabolism in an elderly male cohort. Furthermore, to reveal gender differences in BMD, calcium consumption rates and parameters of bone metabolism according to LCT polymorphism in an existing female cohort. SETTING AND SUBJECTS: A total of 239 men, aged 61+/-9 yr, were available from a former population based study cohort. All men were of Caucasian origin and came from the same region. Blood was sampled for genotyping of the LCT polymorphism and determination of markers of bone metabolism. All participants underwent physical examination, measurement of bone density and completed a standardized calcium questionnaire. Identical procedures had been carried out in a female cohort before (no. 350). RESULTS: Distribution of the LCT genotype in the study cohort was 27% CC (associated with LM; adult-type hypolactasia), 55% TC and 18% TT (lactase persistence). Amounts of total ingested calcium were similar among the three genotype groups. Amounts of consumed milk were generally low in men, LCT polymorphism did not influence rates of milk consumption for men preferred other sources of calcium. BMD, markers of bone metabolism and fracture rates did not differ. General anthropometric characteristics did not differ between the LCT groups either. CONCLUSIONS: Under conditions of low milk intake LCT polymorphism does not alter bone density, markers of bone metabolism and fractures in this cohort of elderly Caucasian men.