Muscle Regeneration and Function in Sports: A Focus on Vitamin D.

Muscle is one of the main targets for the biological effects of vitamin D. This hormone modulates several functions of skeletal muscles, from development to tissue repair after injury, through genomic and non-genomic mechanisms. Vitamin D deficiency and supplementation seem to significantly affect muscle strength in different populations, including athletes, although optimal serum 25(OH)D3 level for sport performance has not been defined so far. Additionally, vitamin D deficiency results in myopathy characterized by fast-twitch fiber atrophy, fatty infiltration, and fibrosis. However, less is known about regenerative effects of vitamin D supplementation after sport-related muscle injuries. Vitamin D receptor (VDR) is particularly expressed in the embryonic mesoderm during intrauterine life and in satellite cells at all stages of life for recovery of the skeletal muscle after injury. Vitamin D supplementation enhances muscle differentiation, growth, and regeneration by increasing the expression of myogenic factors in satellite cells. The objective of this narrative review is to describe the role of vitamin D in sport-related muscle injury and tissue regeneration.

High rate of vertebral refracture after vertebroplasty in patients taking glucocorticoids: a prospective two-year study.

OBJECTIVES: To assess vertebral fracture (VFx) occurrence after percutaneous vertebroplasty (PVP) in patients with osteoporosis (OP), primary or secondary to chronic glucocorticoid (GC) therapy. METHODS: Prospective study of a 2-year follow-up. PRIMARY OUTCOME: proportion of patients with new VFx 24 months after PVP. Eligible patients were osteoporotic patients with VFx and pain resistant to conventional therapy, under GC therapy (n=70) or not (n=71), who underwent PVP. X-rays of dorso/lumbar spine were performed before PVP and 12 and 24 months after the procedure. All the patients were given secondary fractures prevention with oral bisphosphonates plus calcium and vitamin D. RESULTS: The two groups were comparable with respect to male to female ratio, age, BMI, pain score, number of prevalent VFx and their score according to Genant, time interval between VFx and PVP, number of VFx that were treated, vitamin D and PTH plasma levels, and bone mineral density at femur sites. The proportion of patients with new VFx was higher at 12 and 24 months in the group taking GC; at 24 months was 44.3% in GC group and 22.6% in non-GC group (RR 1.96; 95% CI 1.19-3.26, p=0.0087). All new VFx were clinically evident. GC-treated patients had more falls than the patients who were not on GC: 43 falls per 100 pts/y and 32 falls per 100 pts/y, respectively (p<0.05); however, only 4 and 6 falls, respectively, caused a VFx (p=NS). Finally, logistic regression model showed that the increased risk of new VFx was associated with GC use (OR 4.53; 95% CI 1.50-13.69, p=0.0073) and low femoral neck T-scores (OR 3.57; 95% CI 1.82-7.02, p=0.0002). CONCLUSIONS: Patients under treatment with GC show a two-fold increased risk of new VFx after PVP with respect to patients with primary OP. This should be weighed in the individual risk/benefit assessment of the procedure.

The effect of biologic agents on bone homeostasis in chronic inflammatory rheumatic diseases.

Osteoporosis (OP) and increased fracture risk are widely observed comorbidities in chronic inflammatory rheumatic diseases (CIRDs). Improved knowledge of the immune/inflammatory pathways, which characterise the pathophysiology of rheumatoid arthritis (RA) and seronegative spondyloarthropathies (SpA), such as ankylosing spondylitis (AS) and psoriatic arthritis (PsA), have provided the link between inflammation and bone loss, via a complex network of bone cells, T and B cells, pro-inflammatory cytokines such as TNF-α, IL1, IL6, IL17, IL23, costimulator molecules, signalling pathways including both RANKL/RANK/OPG and Wnt signallings. The complex osteoimmunologic network in CIRDs suggested that the powerful anti-inflammatory activity of biologic drugs, beyond the control of the disease, was likely to reduce OP and fracture risk. In this respect, the available data deriving from clinical and experimental studies, conducted with TNF-α, IL6 and IL1 blockers, and B and T cell therapies, have demonstrated a beneficial effect on bone mineral density (BMD) and/or bone turnover markers (BTs). However, whether these drugs are able to positively influence also fracture risk has not yet been established, since the data available are sparse and inconclusive. Thus, systemic bone loss and increased fracture rates still remain relevant comorbidities that should be considered for screening and prevention, and proper treatment of patients with CIRDs despite the biologic therapy.

Retrospective evaluation of persistence in osteoporosis therapy with oral bisphosphonates in Italy: the TOBI study.

The patients' persistence with osteoporosis treatments is low. This retrospective, multicenter survey showed that almost 30% of osteoporotic patients discontinued the treatment within the first 6 months and that those taking drinkable bisphosphonates were less likely to interrupt the therapy; instead, the use of generic bisphosphonates was associated to a more precocious interruption. PURPOSE: Low persistence with osteoporosis medications is associated with higher fracture risk. This study aimed to assess the persistence to treatment with oral bisphosphonates among Italian osteoporotic patients under treatment for at least 6 months and to evaluate whether the different oral formulations of bisphosphonates may influence the interruption of the therapy. METHODS: 723 consecutive osteoporotic patients, aged 50 years or over, referred as outpatients for a follow-up visit after receiving a prescription of an oral bisphosphonate for the first time for at least 6 months were enrolled in this retrospective, multicenter survey carried out under conditions of usual clinical practice. All the patients enrolled were submitted to a standardized interview. RESULTS: 191 patients turned out to have discontinued treatment (28.7%), the more common causes for interruption being the adverse events (43.9%), fear of adverse events (23.3%) and perceived absence of efficacy of the treatment (15.8%). The osteoporotic patients taking drinkable bisphosphonate or on treatment with aromatase inhibitors or under the age of 70 years were less likely to interrupt the treatment. However, these associations were no longer significant when the pharmaceutical formulation (generic vs branded) was included into the multivariate logistic regression model. CONCLUSION: This study suggests that the new drinkable formulations of bisphosphonates could be an interesting option able to reduce upper GI adverse events, thus increasing persistence; whereas the generic formulations of bisphosphonates were associated to a premature discontinuation.

How the knowledge of fracture risk might influence adherence to oral therapy of osteoporosis in Italy: the ADEOST study.

UNLABELLED: The patients' adherence to osteoporosis treatments is low. In our study population a history of osteoporotic fractures was associated to better compliance and persistence; however, a 12-month randomized study carried out on 816 osteoporotic women showed that providing the patients with their individual fracture risk information did not prove effective. PURPOSE: Several drugs are currently available for the treatment of osteoporosis, but the patients' compliance and persistence with these treatments are low. This study aimed to both analyze the adherence to oral osteoporosis medications among Italian osteoporotic patients (cross-sectional study) and evaluate if providing patients with their individual fracture risk information may improve compliance and persistence (prospective study). METHODS: A total of 3379 osteoporotic patients referred as outpatients for a visit 1 year after receiving a prescription of oral osteoporosis medications for the first time, were enrolled for the retrospective study. Moreover, 816 postmenopausal women receiving an oral prescription for osteoporosis for the first time, were randomized into two groups: group 1 (managed according to standard clinical practice) and group 2 (managed with greater patient involvement and information on the individual risk of major osteoporotic fractures calculated by DeFRA algorithm). RESULTS: In the retrospective study, a history of osteoporotic fractures, the frequency of drug administration and a condition of being overweight/obese had a significant influence on both compliance and persistence. Of the 816 patients enrolled in the longitudinal study, 731 (374 of group 1 and 357 of group 2) attended the 1 year follow-up visit. The percentage of women with high compliance or persistence was greater in group 2 (64.2 vs. 58.1 % and 66.8 vs. 62.6 %, respectively), but without reaching any statistical significance. CONCLUSIONS: Although providing the patients with their individual fracture risk information was not statistically effective, further studies on additional interventions able to improve the patients' perceived risk of fracture are warranted.

Determinants and effects of vitamin D supplementation on serum 25-hydroxy-vitamin D levels in patients with rheumatoid arthritis.

OBJECTIVES: Osteoporosis (OP) and increased risk of fracture are relevant features in patients with rheumatoid arthritis (RA). Low levels of serum vitamin D are frequently reported and correlate with a higher RA activity. This study evaluated factors related with the prescription of vitamin D supplements in RA patients and variables influencing the achievement of adequate vitamin D levels. METHODS: Study population was made up by 1168 consecutive RA patients from 22 Italian rheumatology centers. Demographic and clinical variables data were collected and 25OH serum vitamin D was measured in all patients. Insufficient serum 25OH vitamin D levels were defined as values lower than 20 ng/mL. RESULTS: The majority of patients (56.0%) was not taking vitamin D supplements. Among the 514 supplemented patients, 196 (38.1%) were taking insufficient dosages (≤440 IU/day). Variables related with the prescription of supplements were older age, female sex, previous bone density assessment and OP diagnosis. Among the 318 patients using daily supplements ≥800 IU, 88 patients (27.7%) did not reach adequate levels of vitamin D. In these patients a higher HAQ score (OR for 1 point=1.62, 95% CI: 1.06-2.49; p=0.03) and poor sun exposure (OR=2.38, 95% CI: 1.05-5.55; p=0.04) were predictors of vitamin D insufficiency. CONCLUSIONS: Vitamin D deficiency is common in patients with RA, even in patients who are regularly using supplements. Vitamin D supplementation is often ineffective even at the recommended dose of 800 IU/day in more disabled patients.

Efficacy of ibandronate: a long term confirmation.

Data deriving from randomized clinical trials, observational studies and meta-analyses, including treatment regimens unlicensed for use in clinical practice, clearly support that 150 mg once-monthly oral and 3 mg quarterly i.v. doses of ibandronate are associated with efficacy, safety and tolerability; notably both these marketed regimens, which largely correspond to ACE ≥10.8 mg, may in addition provide a significant efficacy on non-vertebral and clinical fracture (Fx) efficacy. The MOBILE and the DIVA LTE studies confirmed a sustained efficacy of monthly oral and quarterly i.v. regimens respectively, over 5 years. Furthermore, improved adherence rates with monthly ibandronate, deriving from studies evaluating large prescription databases, promise to enhance fracture protection and decrease the social and economic burden of postmenopausal osteoporosis.

Genetic epidemiology of Paget's disease of bone in italy: sequestosome1/p62 gene mutational test and haplotype analysis at 5q35 in a large representative series of sporadic and familial Italian cases of Paget's disease of bone.

Families affected by Paget's disease of bone frequently harbor mutations in the SQSTM1/p62 gene. In this multicentric study we collected 345 sporadic and 12 familial PDB cases throughout Italy, identifying 12 different mutations, 5 of which are newly reported and 3, D335E, A381V, and Y383X, external to the UBA domain. Subjects with truncating mutations, E396X, showed a significantly younger age at clinical diagnosis, while the Y383X subjects had a higher average number of affected skeletal sites. All the mutants exhibited the CGTG-H2 haplotype. In two pairs and one triad of unrelated Italian PDB families from different Italian regions, we detected a common SQSTM1/p62 mutation for each P392L, M404V, and G425R group. Since the CGTG-H2 haplotype frequency was also high in normal subjects, and genetic influence due to migratory fluxes of different ethnic groups exists in the Italian population, to refine the search for a more geographically specific founder effect, we extended the haplotype analysis in these families using polymorphic microsatellite repeat markers, within and flanking the SQSTM1/p62 locus, from chromosome 5q35, other than the exon 6 and 3'UTR polymorphisms. All mutant carriers from two of the three M404V families and from the G425R families exhibited common extended chromosome 5q35 haplotypes, IT01 and IT02, respectively, which may be reflecting influences of past migrations. This may be helpful in estimating the true rate of de novo mutations. We confirm the data on the existence of both a mutational hotspot at the UBA domain of SQSTM1/p62 and a founder effect in the PDB population.

Guidelines for the management of osteoporosis and fragility fractures.

The purpose of this document, a result of the harmonisation and revision of Guidelines published separately by the SIMFER, SIOMMMS/SIR, and SIOT associations, is to provide practical indications based on specific levels of evidence and various grades of recommendations, drawn from available literature, for the management of osteoporosis and for the diagnosis, prevention, and treatment of fragility fractures. These indications were discussed and formally approved by the delegates of the Italian Scientific Associations involved in the project (SIE, SIGG, SIMFER, SIMG, SIMI, SIOMMMS, SIR, and SIOT).

Intramuscular neridronate in postmenopausal women with low bone mineral density.

Compliance to osteoporosis treatment with oral bisphosphonates is very poor. Intermittent intravenous bisphosphonate is a useful alternative, but this route is not readily available. Neridronate, a nitrogen-containing bisphosphonate that can be given intramuscularly (IM), was tested in a phase 2 clinical trial in 188 postmenopausal osteoporotic women randomized to IM treatment with 25 mg neridronate every 2 weeks, neridronate 12.5 or 25 mg every 4 weeks, or placebo. All patients received calcium and vitamin D supplements. The patients were treated over 12 months with 2-year posttreatment follow-up. After 12-month treatment, all three doses were associated with significant bone mineral density (BMD) increases at both the total hip and spine. A significant dose-response relationship over the three doses was observed for the BMD changes at the total hip but not at the spine. Bone alkaline phosphatase decreased significantly by 40-55% in neridronate-treated patients, with an insignificant dose-response relationship. Serum type I collagen C-telopeptide decreased by 58-79%, with a significant dose-response relationship (P < 0.05). Two years after treatment discontinuation, BMD declined by 1-2% in each dose group, with values still significantly higher than baseline at both the spine and the total hip. Bone turnover markers progressively increased after treatment discontinuation, and on the second year of follow-up the values were significantly higher than pretreatment baseline. The results of this study indicate that IM neridronate might be of value for patients intolerant to oral bisphosphonates and unwilling or unable to undergo intravenous infusion of bisphosphonates.

Personalization of biologic therapy in patients with rheumatoid arthritis: less frequently accounted choice-driving variables.

OBJECTIVE: To propose appropriate statements that drive the choice of biologic therapies in patients with rheumatoid arthritis (RA), factoring in their impact on the following issues: anti-drug antibody (ADAb) formation, suspicion and management of infections, lupus-like syndrome (LLS), effects on bone mass and sexual sphere, and relationship between RA and periodontal disease (PD). METHODS: An overview of existing evidence was undertaken by an expert panel on behalf of the Italian board for the TAilored BIOlogic therapy (ITABIO). Data were extracted from controlled trials, national registries, national health care databases, post-marketing surveys, and, when required by the paucity of controlled studies, from open-label clinical series. Anti-tumor necrosis factor (anti-TNF) and non-anti-TNF-targeted biologics approved for RA were investigated. RESULTS: ADAb formation is chiefly associated with anti-TNFs, and it is reduced by combination therapy with methotrexate. To date, ADAb titration is not advisable for clinical practice, and, in case of anti-TNF secondary failure, a non-anti-TNF biologic is indicated. LLS is observed in anti-TNF receivers and, in most cases, resolves without anti-TNF withdrawal. A non-anti-TNF biologic is advisable in patients experiencing LLS. Non-anti-TNFs demonstrated a low or absent infection risk and are preferable in patients with comorbidities. Due to their positive effects on bone mass, anti-TNFs are indicated in women at osteoporosis risk, whereas non-anti-TNF have been poorly investigated. The emerging evidence of the relationship between RA and PD and the effects on anti-TNF efficacy should lead clinicians to consider the periodontal status in RA patients. Anti-TNFs may exert a positive effect on fertility and sexuality, and clinicians should explore these aspects in RA patients. CONCLUSION: The optimization of biologic therapies by taking into proper account the above issues would improve patient outcomes.

[Glucocorticoid-induced osteoporosis and rheumatic diseases. Pathogenesis, prevention and treatment]. / Osteoporosi da glucocorticoidi e malattie reumatiche. Patogenesi, prevenzione e trattamento.

Glucocorticoids (GC) are diffusely used to treat a wide variety of inflammatory and autoimmune disorders, including rheumatic diseases. GC-induced osteoporosis (GIO) is the most common and serious side-effect for patients receiving GC. Loss of bone mineral density (BMD) is greatest in the first few months of GC use; fracture (Fx) risk is significantly increased at the spine and hip on doses even as low as 2.5 mg of prednisolone daily; Fx risk increases rapidly from the onset of therapy and, for a given BMD, is higher in GIO than in postmenopausal OP. General measures to reduce bone loss include use of the lowest effective dose; consideration of alternative routes of administration; adequate calcium and vitamin D supplementation. Today, results from large randomised controlled clinical trials provide evidence that bone loss and Fx may be prevented through the use of bone sparing agents (hormone therapy, bisphosphonates, PTH 1-34). Bisphosphonates (alendronate, risedronate) are first-choice therapy for the prevention and treatment of GIO; patients at high risk for Fx, for example those in post-menopausal status or aged > or =65 years and those with a prior fragility Fx, should be advised to start bone-protective therapy at the time of starting GC. Due to the prevalence of GC use, it is imperative that there be a greater awareness of GIO and of therapies that may be offered to patients both for prevention and treatment.

Efficacy of risedronate on clinical vertebral fractures within six months.

OBJECTIVE: Postmenopausal osteoporotic women with pre-existing or new incident vertebral fractures are at high risk for future fracture, so prompt treatment is warranted. Risedronate has been shown to reduce the incidence of radiographically-defined vertebral fractures by approximately two-thirds within 1 year. RESEARCH DESIGN: This study examined the effects of risedronate treatment on the time course of the reduction in the risk of clinical vertebral fractures (i.e., symptomatic fractures), on the risk of moderate-to-severe radiographic vertebral fractures, and on height. RESULTS: In 2442 postmenopausal women with prevalent vertebral fractures from the Vertebral Efficacy with Risedronate Therapy (VERT) studies who received either risedronate 5 mg or placebo, daily risedronate reduced the risk of clinical vertebral fractures within 6 months (RR = 0.08, 95% CI 0.01-0.63), and by 69% at 1 year (RR = 0.31, 95% CI 0.12, 0.78). At 1 year, risedronate also reduced the risk of moderate-to-severe radiographically-defined vertebral fractures by 71% (RR = 0.29 95% CI 0.16, 0.54). Height loss was attenuated with treatment, most notably in patients who experienced new vertebral fractures, with a median difference of 0.73 cm compared with subjects receiving placebo (p = 0.005). CONCLUSION: Risedronate reduces the risk of clinical vertebral fractures in postmenopausal women with osteoporosis within 6 months of commencing treatment.

Adverse events during longterm low-dose glucocorticoid treatment of polymyalgia rheumatica: a retrospective study.

OBJECTIVE: To assess the occurrence of adverse events in a cohort of patients with polymyalgia rheumatica (PMR), treated with low-dose glucocorticoids (GC). METHODS: This was a retrospective study by review of medical records. RESULTS: We identified 222 patients who had a mean duration of followup of 60 ± 22 months and a mean duration of GC therapy of 46 ± 22 months. We found that 95 patients (43%) had at least 1 adverse event after a mean duration of GC therapy of 31 ± 22 months and a mean cumulative dose of 3.4 ± 2.4 g. In particular, 55 developed osteoporosis, 31 had fragility fractures; 27 developed arterial hypertension; 11 diabetes mellitus; 9 acute myocardial infarction; 3 stroke; and 2 peripheral arterial disease. Univariate analysis showed that the duration of GC treatment was significantly associated with osteoporosis (p < 0.0001), fragility fractures (p < 0.0001), arterial hypertension (p < 0.005), and acute myocardial infarction (p < 0.05). Cumulative GC dose was significantly associated with osteoporosis (p < 0.0001), fragility fractures (p < 0.0001), and arterial hypertension (p < 0.01). The adverse events occurred more frequently after 2 years of treatment. Multivariate analysis showed that GC duration was significantly associated with osteoporosis (adjusted OR 1.02, 95% CI 1.02-1.05) and arterial hypertension (adjusted OR 1.03, 95% CI 1.01-1.06); GC cumulative dose was significantly associated with fragility fractures (adjusted OR 1.4, 95% CI 1.03-1.8). CONCLUSION: Longterm, low-dose GC treatment of PMR is associated with serious adverse events such as osteoporosis, fractures, and arterial hypertension; these adverse events occur mostly after 2 years of treatment.

Vitamin D deficiency in rheumatoid arthritis: prevalence, determinants and associations with disease activity and disability.

INTRODUCTION: The aim of this study was to estimate the prevalence and determinants of vitamin D deficiency in patients with rheumatoid arthritis (RA) as compared to healthy controls and to analyze the association between 25-hydroxyvitamin D (25(OH)D) with disease activity and disability. METHODS: The study includes 1,191 consecutive RA patients (85% women) and 1,019 controls, not on vitamin D supplements, from 22 Italian rheumatology centres. Together with parameters of disease activity, functional impairment, and mean sun exposure time, all patients had serum 25(OH)D measured in a centralized laboratory. RESULTS: A total of 55% of RA patients were not taking vitamin D supplements; the proportion of these with vitamin D deficiency (25(OH)D level <20 ng/ml) was 52%. This proportion was similar to that observed in control subjects (58.7%). One third of supplemented patients were still vitamin D deficient. In non-supplemented RA patients 25(OH)D levels were negatively correlated with the Health Assessment Questionnaire Disability Index, Disease Activity Score (DAS28), and Mobility Activities of daily living score. Significantly lower 25(OH)D values were found in patients not in disease remission or responding poorly to treatment, and with the highest Steinbrocker functional state. Body mass index (BMI) and sun exposure time were good predictors of 25(OH)D values (P < 0.001). The association between disease activity or functional scores and 25(OH)D levels remained statistically significant even after adjusting 25(OH)D levels for both BMI and sun exposure time. CONCLUSIONS: In RA patients vitamin D deficiency is quite common, but similar to that found in control subjects; disease activity and disability scores are inversely related to 25(OH)D levels.

Single infusion of neridronate (6-amino-1-hydroxyhexylidene-1,1-bisphosphonate) in patients with active rheumatoid arthritis: effects on disease activity and bone resorption markers.

AIMS: The aim of this study was to assess the effects of a single infusion of the bisphosphonate neridronate (N) on parameters of inflammation and bone resorption in rheumatoid arthritis (RA). METHODS: Forty-five patients with active RA were randomly allocated on a double blind basis to receive a single intravenous infusion of either N 25 mg (15 patients), N 50 mg (15 patients), or placebo (15 patients). At baseline and after 7 and 21 days, we assessed the following: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and Ritchie's articular index as indices of disease activity; and urinary free deoxypyridinoline (DPyr), N-telopeptide of type I collagen (NTx) and hydroxyproline (OHP) as indices of bone resorption. RESULTS: At day 7, N 25 mg significantly decreased ESR compared to N 50 mg (p=0.002), and CRP compared to placebo (p=0.036). With regard to bone resorption markers, at day 7, both N 25 mg and 50 mg compared to placebo significantly decreased NTx (p<0.0005 and p=0.003, respectively) and OHP (p=0.001 and p=0.004, respectively). At day 21, N 50 mg significantly decreased OHP compared to placebo (p=0.017). DPyr levels remained unchanged in the three groups. CONCLUSIONS: N 25 mg and 50 mg exerted different effects on RA activity parameters, since only the lower dose significantly decreased ESR and CRP. Both doses of N inhibited bone resorption, with a transient, significant reduction in urinary NTx and OHP, but without any effect on DPyr.

The effect of age, weight, and lifestyle factors on calcaneal quantitative ultrasound: the ESOPO study.

Quantitative ultrasound (QUS) techniques have been shown to be as good as bone mineral density (BMD) assessed by dual-energy X-ray absorptiometry (DXA), in predicting fracture risk: QUS technique could increase substantially the accessibility to a reliable bone osteoporosis risk evaluation, but little is know regarding the relationship of QUS to risk factors that have been found to predict DXA-BMD values and this is even more true in men. We studied 6,811 postmenopausal women 40 to 80 years of age and 4,981 men 60-80 years of age representative of the general population of all regions of Italy. All participants were questioned on lifestyle habits and on their medical history. After a physical examination "bone stiffness" (called here for simplicity, stiffness), which is derived from the values of broadband ultrasound attenuation (BUA) and speed of sounds (SoS) was measured by a heel QUS device (Achilles apparatus, Lunar, Madison, USA). The most common recognized determinants of bone mass (either categorical or continuous variables) were modeled with stiffness by multiple regression analysis or ANOVA. Stiffness was strongly related to age and weight. After adjusting for these variables, the women who had taken hormone replacement therapy for more than a year had significantly higher stiffness values. The difference versus nonusers remained significant for up to 20 years-since-menopause (YSM). This effect was so strong that for further analysis these women were excluded. By multivariate analysis, stiffness was then found to be significantly related to recalled body weight at 25 years of age, actual and past cigarettes smoked per day, and dairy calcium intake. Stiffness was also associated with a number of categorial factors adjusted for age, weight, and YSM: prior ovariectomy, history of more than 2 months confined to bed, outdoor physical activity, smoking, chronic use of any drug, and past corticosteroid use. All these categorial and continuous variables predicted stiffness equally in men and women. In conclusion, QUS bone measurements discriminate postmenopausal women according to past use of hormone replacement therapy. Risk factors usually associated to BMD as measured by DXA are also associated to calcaneal bone stiffness as measured by QUS, and most risk factors for osteoporosis usually observed in women are equally applicable to men.

Effect of low dose methotrexate on bone density in women with rheumatoid arthritis: results from a multicenter cross-sectional study.

OBJECTIVE: To analyze the influence of low dose methotrexate (MTX) on bone using data from a large multicenter, cross-sectional study on bone mineral density (BMD) in women with rheumatoid arthritis (RA). METHODS: We selected 731 female patients with RA divided into 2 groups on the basis of MTX use: never MTX users (n = 485) and MTX users for at least 6 months (n = 246). Demographic, disease, and treatment related variables were collected for each patient. BMD was measured at lumbar spine and proximal femur by dual energy x-ray absorptiometry. Osteoporosis was defined as BMD < -2.5 T-score. RESULTS: The frequency of osteoporosis among never MTX users and MTX users was 29.1% and 28.3% (p = NS) for lumbar spine, and 34.8% and 37.8% (p = NS) for femoral neck, respectively. Mean T-score values at lumbar spine and femoral neck were comparable in the 2 groups, even after adjusting for age, menopausal status, body mass index (BMI), Health Assessment Questionnaire (HAQ) score, and steroid use. The generalized linear model showed that age, menopause, BMI, HAQ score, and steroid use were significant independent predictors of BMD at lumbar or at femoral level, whereas MTX use was not. Logistic procedure showed that only age, HAQ score, and BMI were significantly associated with the risk of osteoporosis. CONCLUSION: We found no negative effect of low dose MTX on BMD in women with RA.