Genetic and environmental determinants of bone quality: a cross-sectional analysis of the Hungarian Twin Registry.

There is abundant evidence that bone mineral content is highly heritable, while the heritability of bone quality (i.e. trabecular bone score [TBS] and quantitative ultrasound index [QUI]) is rarely investigated. We aimed to disentangle the role of genetic, shared and unique environmental factors on TBS and QUI among Hungarian twins. Our study includes 82 twin (48 monozygotic, 33 same-sex dizygotic) pairs from the Hungarian Twin Registry. TBS was determined by DXA, QUI by calcaneal bone ultrasound. To estimate the genetic and environmental effects, we utilized ACE-variance decomposition. For the unadjusted model of TBS, an AE model provided the best fit with > 80% additive genetic heritability. Adjustment for age, sex, BMI and smoking status improved model fit with 48.0% of total variance explained by independent variables. Furthermore, there was a strong dominant genetic effect (73.7%). In contrast, unadjusted and adjusted models for QUI showed an AE structure. Adjustments improved model fit and 25.7% of the total variance was explained by independent variables. Altogether 70-90% of the variance in QUI was related to additive genetic influences. We found a strong genetic heritability of bone quality in unadjusted models. Half of the variance of TBS was explained by age, sex and BMI. Furthermore, the adjusted model suggested that the genetic component of TBS could be dominant or an epistasis could be present. In contrast, independent variables explained only a quarter of the variance of QUI and the additive heritability explained more than half of all the variance.

The effect of COVID-19 vaccination status on all-cause mortality in patients hospitalised with COVID-19 in Hungary during the delta wave of the pandemic.

The high mortality of patients with coronavirus disease 2019 (COVID-19) is effectively reduced by vaccination. However, the effect of vaccination on mortality among hospitalised patients is under-researched. Thus, we investigated the effect of a full primary or an additional booster vaccination on in-hospital mortality among patients hospitalised with COVID-19 during the delta wave of the pandemic. This retrospective cohort included all patients (n = 430) admitted with COVID-19 at Semmelweis University Department of Medicine and Oncology in 01/OCT/2021-15/DEC/2021. Logistic regression models were built with COVID-19-associated in-hospital/30 day-mortality as outcome with hierarchical entry of predictors of vaccination, vaccination status, measures of disease severity, and chronic comorbidities. Deceased COVID-19 patients were older and presented more frequently with cardiac complications, chronic kidney disease, and active malignancy, as well as higher levels of inflammatory markers, serum creatinine, and lower albumin compared to surviving patients (all p < 0.05). However, the rates of vaccination were similar (52-55%) in both groups. Based on the fully adjusted model, there was a linear decrease of mortality from no/incomplete vaccination (ref) through full primary (OR 0.69, 95% CI: 0.39-1.23) to booster vaccination (OR 0.31, 95% CI 0.13-0.72, p = 0.006). Although unadjusted mortality was similar among vaccinated and unvaccinated patients, this was explained by differences in comorbidities and disease severity. In adjusted models, a full primary and especially a booster vaccination improved survival of patients hospitalised with COVID-19 during the delta wave of the pandemic. Our findings may improve the quality of patient provider discussions at the time of admission.

Comparison of Efficacy and Safety of Commercially Available Fixed-Ratio Combinations of Insulin Degludec/Liraglutide and Insulin Glargine/Lixisenatide: A Network Meta-analysis.

OBJECTIVES: Our aim in this study was to compare the efficacy and safety of commercially available fixed-ratio combinations (FRCs) of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and basal insulins by a network meta-analysis of randomized controlled trials (RCTs) of people with type 2 diabetes. METHODS: We present a systematic review and network meta-analyses of RCTs of individuals with type 2 diabetes randomized to FRCs or to their components for ≥24 weeks. All reports were obtained from PubMed or ClinicalTrials.gov up to February 28, 2022. The primary outcome was glycated hemoglobin (A1C) level attained. Secondary outcomes included fasting plasma glucose, change in body weight, and incident hypoglycemia. Treatment effects were estimated as mean difference (MD) and standard error (SE), or as odds ratio (OR) with 95% confidence interval (CI) using the fixed combination of insulin glargine 100 IU/mL and lixisenatide (iGlarLixi) as reference. RESULTS: We included 29 RCTs from among the 1,404 articles identified. No direct comparisons between FRCs were found. After excluding some insulin-capped trials to reach model consistency, both FRCs were more efficacious regarding A1C than their components, but no difference between FRCs was found (MD, -0.10%; SE, 0.10%). The effect of the fixed combination of insulin degludec and liraglutide (IDegLira) (MD, -0.47 mmol/L; SE, 0.24 mmol/L) and basal insulins was similar to that of iGlarLixi (reference) on fasting glucose, whereas GLP-1RAs had lower efficacy than iGlarLixi. Weight gain was lower with GLP-1RAs and IDegLira (MD, -0.72 kg; SE, 0.32 kg) than with iGlarLixi (reference) and higher with basal insulins. Incident hypoglycemia (based on different definitions) was least frequent with GLP-1RAs, followed by IDegLira (OR, 0.78; 95% CI, 0.39 to 1.57), iGlarLixi (reference), and basal insulins. CONCLUSIONS: For A1C, both FRCs were more efficacious over their individual components, with similar efficacies of the 2 FRCs.

Utilizing Graphical Analysis of Chest Radiographs for Primary Screening of Osteoporosis.

Background and Objectives: Osteoporosis is a major risk of fractures, harming patients' quality of life. Dual-energy X-ray absorptiometry (DXA), which can detect osteoporosis early, is too expensive to be conducted on a regular basis. Therefore, we aimed to evaluate a screening method using chest radiographs developed in Japan applied to another population. Materials and Methods: Fifty-five patients who had a chest radiograph and DXA and applied within three months of each test were recruited from the patient database of Semmelweis University (Budapest, Hungary). Graphical analysis of the chest radiographs was conducted to identify the ratio of the cortical bone in the clavicle of each patient. Two researchers performed the analysis, and multiple regression was conducted to determine the bone mineral density of each patient provided by DXA. Results: The Pearson correlation between two examiners' determinations of the cortical bone ratio was 0.769 (p < 0.001). The multiple regression model proved to be statistically significant in identifying osteoporosis, but the model adopted for the Hungarian population was different compared to the Japanese population. Conclusions: This simple, economic Japanese graphical analysis method for chest radiographs may be feasible in detecting osteoporosis. Further studies with a larger population of patients with greater variety of ethnicity would be of value in improving the accuracy of this model.

Different patterns of excess all-cause mortality by age and sex in Hungary during the 2nd and 3rd waves of the COVID-19 pandemic.

It is well accepted that COVID-19-related mortality shows a strong age dependency. However, temporal changes in the age distribution of excess relative mortality between waves of the pandemic are less frequently investigated. We aimed to assess excess absolute mortality and the age-distribution of all-cause mortality during the second and third waves of the COVID-19 pandemic in Hungary compared to the same periods of non-pandemic years. Rate ratios for excess all-cause mortality with 95% confidence intervals and the number of excess deaths for the second (week 41 of 2020 through week 4 of 2021) and third waves (weeks 7-21 of 2021) of the COVID pandemic for the whole of Hungary compared to the same periods of the pre-pandemic years were estimated for 10-year age strata using Poisson regression. Altogether, 9771 (95% CI: 9554-9988) excess deaths were recorded during the second wave of the pandemic, while it was lower, 8143 (95% CI: 7953-8333) during the third wave. During the second wave, relative mortality peaked for ages 65-74 and 75-84 (RR 1.37, 95%CI 1.33-1.41, RR 1.38, 95%CI 1.34-1.42). Conversely, during the third wave, relative mortality peaked for ages 35-44 (RR 1.43, 95%CI 1.33-1.55), while those ≥65 had substantially lower relative risks compared to the second wave. The reduced relative mortality among the elderly during the third wave is likely a consequence of the rapidly increasing vaccination coverage of the elderly coinciding with the third wave. The hugely increased relative mortality of those 35-44 could point to non-biological causes, such as less stringent adherence to non-pharmaceutical measures in this population.

Association of childhood fractures with osteoporosis of the elders: a coincidence or a forecast? / A gyermekkori csonttörések kapcsolata az idoskori osteoporosissal: véletlen vagy elorejelzés?

Összefoglaló. A gyermekek közel fele szenved el csonttörést. Ez lehet traumás esemény vagy a csontfejlodést megzavaró genetikus, hormonális vagy egyéb eltérés a csontváz bármely részén. A leggyakoribb azonban az enyhe trauma kapcsán jelentkezo csuklótáji törés, amely többnyire a pubertas alatt fordul elo. A jelenség alapja, hogy a serdülés során átmenetileg elválik egymástól a csontok méretének gyors növekedése és a csonttömeg gyarapodása, ami a longitudinális növekedést kb. egy év késéssel követi. Az így kialakuló átmeneti csontgyengeség a gyermekkori csonttörés fo oka, aminek a hatásához az említett genetikai, hormonális és életmódi rendellenességek is csatlakozhatnak. A gyermekkorban elofordult kistraumás csonttörés a felnott férfiaknál az osteoporosisos csonttörések fokozott rizikójával jár, ezért szurovizsgálati kérdésként is szolgál. Nok esetében ugyanez az összefüggés még bizonyításra vár. Orv Hetil. 2021; 162(42): 1687-1692. Summary. Bone fracture occurs nearly in half of the children. Some fractures are severe traumatic events while others are the results of genetic or hormonal or other alterations disturbing the normal development of bone. However, the majority of fractures are associated with a mild trauma, dominantly in the pubertal period. The basic pathology of the pubertal fractures is the transient deviation of peak velocity of height growth from the gain velocity of bone mass; the latter goes to peak 1 year later than height growth. This difference has been resulted in a physiologic but transient weakening of bones that can coincide with genetic, hormonal or life-style problems and all of these factors together may cause the increased fragility of the pubertal bone. Low-trauma fractures in childhood may be followed in high fracture risk of adult and aging men, so the childhood fracture seems to be a useful screening question for testing the osteoporosis in males. However, the same relation is still not proved in aging women. Orv Hetil. 2021; 162(42): 1687-1692.

Association of Cardiovascular Autonomic Neuropathy and Distal Symmetric Polyneuropathy with All-Cause Mortality: A Retrospective Cohort Study.

BACKGROUND: People with diabetic cardiovascular autonomic neuropathy (CAN) have increased cardiovascular mortality. However, the association between distal symmetric polyneuropathy (DSPN) or CAN with all-cause mortality is much less investigated. Thus, we set out to examine the effect of CAN and DSPN on all-cause mortality in a well-phenotyped cohort. METHODS: All diabetes cases (n = 1,347) from the catchment area of a secondary diabetes care centre who had medical examination including neuropathy assessment between 1997 and 2016 were followed up for all-cause mortality in the NHS Hungary reimbursement database until 2018. We investigated the association of CAN (Ewing tests) and DSPN (Neurometer) with all-cause mortality using Cox models stratified by diabetes type. RESULTS: Altogether, n = 131/1,011 persons with type 1/type 2 diabetes were included. Of the participants, 53%/43% were male, mean age was 46 ± 12/64 ± 10 years, diabetes duration was 13 ± 10/7 ± 8 years, 42%/29% had CAN, and 39%/37% had DSPN. During the 9 ± 5/8 ± 5-year follow-up, n = 28/494 participants died. In fully adjusted models, participants with type 1 diabetes patients with versus without DSPN had an increased mortality (HR 2.99, 95% CI 1.4-8.63), while no association with CAN was observed. In type 2 diabetes, both DSPN and CAN independently increased mortality (HR 1.32, 95% CI: 1.07-1.64, and HR 1.44, 95% CI: 1.17-1.76). CONCLUSIONS: Our results are compatible with an increased risk of mortality in people with type 1 diabetes and DSPN. Furthermore, we report a similarly strong association between DSPN and CAN and all-cause mortality in type 2 diabetes mellitus.

Strong Genetic Effects on Bone Mineral Density in Multiple Locations with Two Different Techniques: Results from a Cross-Sectional Twin Study.

Background and Objectives: Previous studies have demonstrated that risk of hip fracture is at least partly heritable. The aim of this study was to determine the magnitude of the genetic component of bone mineral density (BMD), using both X-ray and ultrasound assessment at multiple sites. Materials and Methods: 216 adult, healthy Hungarian twins (124 monozygotic, MZ, 92 dizygotic, DZ; mean age 54.2 ± 14.3 years), recruited from the Hungarian Twin Registry with no history of oncologic disease underwent cross-sectional BMD studies. We measured BMD, T- and Z-scores with dual energy X-ray absorptiometry (DEXA) at multiple sites (lumbar spine, femoral neck, total hip and radius). Quantitative bone ultrasound (QUS) was also performed, resulting in a calculated value of estimated bone mineral density (eBMD) in the heel bone. Heritability was calculated using the univariate ACE model. Results: Bone density had a strong genetic component at all sites with estimates of heritability ranging from 0.613 to 0.838 in the total sample. Lumbar BMD and calcaneus eBMD had major genetic components with estimates of 0.828 and 0.838 respectively, and least heritable (0.653) at the total hip. BMD of the radius had also a strong genetic component with an estimate of 0.806. No common environmental effect was found. The remaining variance was influenced by unique environment (0.162 to 0.387). In females only, slightly higher additive genetic estimates were found, especially in the case of the femoral neck and total hip. Conclusion: Bone mineral density is strongly heritable, especially in females at all locations using both DEXA and QUS, which may explain the importance of family history as a risk factor for bone fractures. Unshared environmental effects account for the rest of the variance with slight differences in magnitude across various bone regions, supporting the role of lifestyle in preventing osteoporotic fractures with various efficacy in different bone regions.

Influence of local exposure to static magnetic field on pain perception and bone turnover of osteoporotic patients with vertebral deformity - a randomized controlled trial.

PURPOSE: Static magnetic field (SMF) could improve pain sensation and bone turnover. In a single-center randomized double-blind placebo-controlled study we investigated the effects of SMF exposure on subjective pain and bone turnover. MATERIALS AND METHODS: Postmenopausal osteoporotic women (aged 50-70 years) with bone deformity and back pain were randomized to 10 weekly visits of 30-min SMF (n = 6) or treatment with non-magnetized pads (n = 5) on the back. Primary and secondary outcomes were changes in pain sensation on a visual analogue scale (VAS) during each visit and over 10 weeks, respectively. Tertiary outcomes were changes in osteocalcin and ß-crosslaps. SMF was inhomogeneous with 192 millitesla peak-to-peak value by 19 tesla/meter gradient of the magnetic flux density at 3 mm. RESULTS: Participants randomized to sham had higher VAS at baseline (mean difference: 2.8, 95% confidence interval (CI) 0.47-5.2 cm). Both SMF and sham similarly reduced short term pain (sham-SMF: 0.59, 95% CI - 0.31-1.49 cm, p = 0.195). VAS did not change in SMF, while it decreased in the sham group (between-group difference 0.27, 95% CI 0.04-0.50 cm/visit). Bone turnover markers remained stable. CONCLUSIONS: SMF as used in this investigation is not recommended for pain relief in postmenopausal women with vertebral deformity. The finding on long-term pain relief may relate to unbalanced randomization.

Calcaneous quantitative ultrasound measurements predicts vertebral fractures in idiopathic male osteoporosis.

OBJECTIVES: The aim of this study was to identify the differences in ultrasound bone variables (QUS) and to test the ability to discriminate male patients with and without vertebral fractures. METHODS: We therefore measured broadband ultrasound attenuation (BUA) and speed of sound (SOS) matched for bone mineral density (BMD) and vertebral deformity in idiopathic male osteoporosis. RESULTS: One hundred and seventeen men (age 56.6 range 27-78) were divided into three groups (osteoporosis n=25, osteopenia n=58 and age-matched control n=34) according to BMD T-score by WHO criteria. We found 66 patients (56%) with at least one vertebral deformity during the study. BMD and BUA did not differ, while SOS was lower in osteoporosis (p<0.001) and control group (p<0.001) between the patients with and without vertebral compression. Strong positive correlation was demonstrated between BUA and BMD (lumbar spine r=0.44, p<0.001, femoral neck r=0.56, p<0.001, radius r=0.40, p<0.001), while similar association between SOS and BMD values was not shown. There was no relationship between the BUA and vertebral fracture risk (Odds ratio: 1.14 95% CI: 0.80-1.61). However, the relative risk of vertebral fracture by SOS was 1.56 (95% CI: 1.08-2.62). Adjusting for age and BMI the risk of vertebral fracture did not change (odds ratio for SOS 1.50 95% CI: 1.02-2.22). After adjustment for BMD SOS was still associated with fracture risk at all measured sites (odds ratio: 1.43, 95% CI: 1.02-2.22; 1.41, 95% CI: 1.02-2.17 and 1.32, 95% CI: 1.02-2.0). CONCLUSION: Our results suggest that BUA values are more closely related to density and structure while SOS values are able to predict fractures.

Comparative evaluation of local and international reference databases for forearm densitometry: different impacts on diagnostic decisions.

Reference databases play a key role in the management of osteoporosis. The aim of this preliminary study was to compare the diagnostic consequences of using either an international or a local reference database in peripheral densitometry. For this purpose, standard curves for bone mineral density (measured by dual-energy X-ray absorptiometry at the distal and proximal forearm) were generated for healthy Hungarian men and women. In total, 303 healthy volunteers of both sexes (age range: 20-94 yr) were recruited from four osteoporosis centers. Subjects with medical conditions or taking medication affecting the bone metabolism were excluded. Bone densitometry was performed with pDEXA (Norland-Stratec, Fort Atkinson, WI) devices in each center after cross-calibration of the machines. The precision error of the forearm measurement was also determined (<1% in vitro, and 1.2-2.5% in vivo). In females, the peak forearm density was detected in the 30-39-yr group. The density decreased by 8% per 5 yr in early postmenopausal females, and by 10% per 10 yr in late postmenopausal females. In males, the highest bone mineral density was found in the 30-39-yr group for the distal forearm, but 1 decade later for the proximal site. Subsequently, a 5% decrease in density occurred per 10 yr, except in the 8th decade, in which a 20% decrease was demonstrated. One thousand four hundred thirty-four patients with suspected osteoporosis were classified according to the forearm density T-scores using both the new Hungarian reference database and the international database provided by the manufacturer. Comparison of the results measured at the distal forearm with the two different databases led to similar outcomes. However, at the proximal site, one fifth of the female patients were reclassified from the low-density group to the normal group using the domestic normative database. An opposite difference was observed for the males: use of the Hungarian reference data resulted in 40% more men being categorized in the low-density group than when the international normal database was applied. Our results suggest that not only geographic differences, but also the reference database used, can influence the prevalence of the diagnosis of osteoporosis. Further data are currently being collected to increase the statistical power of the study.

Comparison of the femoral neck bone density, quantitative ultrasound and bone density of the heel between dominant and non-dominant side.

Our study was initiated to evaluate whether there are differences between the two sides, depending on hand dominance, in densitometry values and quantitative ultrasound parameters (QUS) of the lower limb. One hundred and six women and 44 men were involved. The hand dominance was determined by interview. The bone mineral density (BMD) of the left and the right femoral necks and the calcanei were measured by dual-energy X-ray absorptiometry (DXA). The QUS examination consisted of measuring the attenuation (BUA), the speed of the ultrasound (SOS) and quantitative ultrasound index (QUI) transversing the left and right calcanei. The density of the neck of femur of the non-dominant side did not differ from that of the dominant side. On the other hand, BMD, BUA and the QUI of the calcaneus were higher on the non-dominant side in both genders (p<0.05 for each parameter). No similar differences were seen for the SOS values. Our study has confirmed the side-to-side differences of the calcaneus in both genders, lower values were found on the dominant side. No similar differences were seen on the femur. The AUC values seemed to be higher on the dominant side, however, these differences were not strictly significant. In the case of peripheral site (heel) measurements, the practical significance of our observations is that they raise the possibility of performing peripheral DXA and QUS examinations of the calcaneus on the dominant side of the patient according to handedness.

[Effect of cigarette smoking on bone quality parameters in women]. / A dohányzás hatása a nok csontjának minoségi jellemzoire.

INTRODUCTION: Smoking is a risk factor for osteoporosis. In a previous study, the authors showed lower bone density among smokers in a group of postmenopausal women. AIMS: After this finding, the primary goal of current research was to investigate how smoking could influence bone quality. METHODS: Forty-five (age range: 25-72 ys) smoker women were compared with 45 nonsmoker women adjusted for age and anthropometric parameters. Quantitative ultrasound method was used to determine the speed of ultrasound and the ultrasound attenuation transmitting the left heel (Achilles In Sight, GE Lunar). Dual photon absorptiometry method was applied to investigate the bone mineral density of lumbar spine and left femoral neck (Prodigy, GE Lunar) and single photon absorptiometry was used to determine the bone mineral content of radius at the non dominant side (NK-364, Gamma). RESULTS: No difference was found between smokers and non-smokers among the premenopausal group, however, postmenopausal smoker women had slightly lower speed of ultrasound and ultrasound attenuation values than non-smoker women. Postmenopausal smoker women suffering from bone fracture had significantly lower speed of ultrasound than postmenopausal non-smoker women (1508.9 vs. 1525.3 m/s, respectively), despite their bone density did not differ from each other. CONCLUSION: These data augment the knowledge about the injurious effect of smoking. The increased risk for bone fracture among smokers could be explained not only with the decrease of bone mass, which was previously described, but also with a decreased bone elasticity.

Increased bone fracture prevalence in postmenopausal women suffering from pollen-allergy.

INTRODUCTION: Our aim was to investigate whether pollen-allergy can affect bone mass and fractures in postmenopausal women. METHODS: A total of 125 postmenopausal pollen-allergic women (mean age: 61.26 yr) were split into four groups: (1) treated with neither H1 histamine receptor (H1R) antagonist nor inhaled corticosteroid (n=43); (2) treated only with H1R antagonist (n=53); (3) treated with both H1R antagonist and inhaled corticosteroid (n=17); (4) treated with only inhaled corticosteroid (n=12). Treatment, in the appropriate groups, had occurred for at least 5 years, seasonally. One-hundred non-allergic postmenopausal subjects matched for age, body mass index (BMI), and age at menopause served as controls. RESULTS: Overweight and obesity (25 kg/m(2) < or =BMI) were common among the allergic women (76%). Allergic patients without treatment had a slightly lower bone density than their non-allergic counterparts. The rate (34.9%) of prevalent low-energy fractures (distal forearm, hip, and clinical vertebral fractures) in untreated allergic patients was almost triple that observed in non-allergic women (13%, chi(2) p=0.003). Bone fracture occurred more often in H1R-only treated patients (30.19%) than in controls (chi(2) p=0.01); however, clinical vertebral or hip fractures developed neither in those treated only with H1R antagonist nor in those who received both H1R antagonist and inhaled corticosteroid. Bone fractures were more frequent among patients with inhaled steroid treatment than among patients with a combined treatment of inhaled steroid and antihistamine (50 versus 29.4%). BMI predicted prevalent fractures at 1.278 (95% CI: 1.047-1.559, p=0.016) for a 1 kg/m(2) increase among untreated allergic patients. CONCLUSION: In conclusion, we found a high prevalence of low-energy fractures among pollen-allergic postmenopausal women which was associated with obesity. It is possible that the H1R antagonists compensate for both the negative effect of pollen-allergy and the adverse effect of inhaled corticosteroid treatment on bone fracture risk.

[Effects of body mass index on bone mineral density in men]. / Testtömeg hatása a férfiak csonttömegére.

INTRODUCTION: A strong positive association between body mass index and bone mineral density is well defined in postmenopausal osteoporosis, but not in men. AIMS: The primary goal of the current research was to investigate this association in case of men. METHODS: According to WHO criteria (T-score below -1.0 at all measure site) seventy-two (mean age 55.7 +/- 0.99, range 38-78 yr normal density) healthy male with normal density were recruited. Exclusion criteria were the absence of any risk factors or signs of metabolic disease. Bone mineral measurements at the lumbar spine (L2-4) and femoral neck were performed by the dual-energy X-ray absorptiometry (DEXA, Lunar DPX-L, USA), bone mineral content of the non-dominant radius was measured with single photon absorptiometry (SPA, NK-364, Hungary). Participants were divided into three groups according to body mass index normal weight (18.5-24.9 kg/m2), moderate overweight (25-29.9 kg/m2) and obese subjects (> 30 kg/m2). RESULTS: Femur neck density was significantly lower in the normal weight than in the overweight counterparts (0.969 +/- 0.03 vs 1.062 +/- 0.02 p = 0.01). There was a strong positive association between BMI and femur neck BMD (r = 0.412 p < 0.001). Body mass was an independent predictor of femur neck bone mineral density (regression coefficients 0.382, p = 0.001). There was not correlation at the lumbar spine and the radius sites. CONCLUSION: Bone density at femur neck sites is lower in the normal weight men than in obese subjects, therefore the risk factors for proximal femur osteoporosis are higher in these cases. Prevention strategy is needed for men in the lowest quintile of body mass to prevent further decrease in BMD and reduce the risk of hip fracture.

The effect of intranasal salmon calcitonin therapy on bone mineral density in idiopathic male osteoporosis without vertebral fractures--an open label study.

The aim of this study was to examine the effect of intranasal salmon calcitonin therapy on bone mineral density (BMD) in idiopathic male osteoporosis without vertebral fractures. We conducted a randomized, open label, controlled trial in 71 male patients (mean age 59 +/- 6 years) suffering from idiopathic osteoporosis (femoral neck T-score < -2.5) without vertebral deformity. Patients in the control group (n = 31) received 400 IU Vitamin D + 1000 mg elemental calcium daily while the treatment group (n = 40) received 400 IU Vitamin D, 1000 mg elemental calcium plus 200 IU calcitonin nasal spray daily during alternate months. The study period was 18 months. Compared to controls, nasal calcitonin was associated with significant increases in bone mineral density at the lumbar spine (+3.5 +/- (-4.3%) vs. +0.83 +/- 6.4%, P = 0.04) and the femoral neck (+3.2 +/- 3.9% vs. +0.68 +/- 5.7%, P = 0.004). No significant difference was observed at the radius between the treatment groups (+1.4 +/- 8.8% vs. +1.4 +/- 10.9%, P = 0.98). Treatment was well tolerated with no premature discontinuations or significant side effects compared to the control group. We conclude that 200 IU salmon calcitonin nasal spray used daily, intermittently proved to be an effective and safe therapy in male idiopathic osteoporosis.

Bone disorders in experimentally induced liver disease in growing rats.

AIM: To investigate the change of bone parameters in a new model of experimentally induced liver cirrhosis and hepatocellular carcinoma (HCC) in growing rats. METHODS: Fischer-344 rats (n = 55) were used. Carbon tetrachloride (CCl(4)), phenobarbital (PB), and a single diethylnitrosamine (DEN) injection were used. Animals were killed at wk 8 and 16. Bone mineral content, femoral length, cortical index (quotient of cortical thickness and whole diameter) and ultimate bending load (F(max)) of the femora were determined. The results in animals treated with DEN+PB+CCl(4) (DPC, n = 21) were compared to those in untreated animals (UNT, n = 14) and in control group treated only with DEN+PB (DP, n = 20). RESULTS: Fatty liver and cirrhosis developed in each DPC-treated rat at wk 8 and HCC was presented at wk 16. No skeletal changes were found in this group at wk 8, but each parameter was lower (P<0.05 for each) at wk 16 in comparison to the control group. Neither fatty liver nor cirrhosis was observed in DP-treated animals at any time point. Femoral length and F(max) values were higher (P<0.05 for both) in DP-treated animals at wk 8 compared to the UNT controls. However, no difference was found at wk 16. CONCLUSION: Experimental liver cirrhosis and HCC are accompanied with inhibited skeletal growth, reduced bone mass, and decreased mechanical resistance in growing rats. Our results are in concordance with the data of other studies using different animal models. A novel finding is the transiently accelerated skeletal growth and bone strength after a 8-wk long phenobarbital treatment following diethylnitrosamine injection.