Safety and effects of calcifediol 0.266 milligrams soft capsules monthly and cholecalciferol 25000 international units monthly in osteoporotic women undergoing therapy with alendronate: a cross-sectional study.

BACKGROUND: The role of vitamin D in human physiology is a topic of great interest for the scientific community in the last decades. The common target for all clinicians is to improve its status in order to prevent several pathological conditions. METHODS: The aim of our study was to evaluate the safety and the efficacy of both calcifediol and cholecalciferol in combination with alendronate in osteoporotic women. A homogeneous population of 300 postmenopausal osteoporotic women was selected for this study. 150 women were administered with alendronate 70 mg combined with clacifediol 0.266 mg soft capsules monthly. The other half (other 150 women) were administered with alendronate 70 mg combined with cholecalciferol 25000 IU monthly. First follow-up was after 4 months and second follow-up after 12 months. RESULTS: No case of toxicity was detected throughout the study in any patient. In regards to increase of vitamin D serum level, after four months supplementation calcifediol is 1.29 fold more effective than cholecalciferol while after 12 months of supplementation calcifediol is 2.32 fold more effective compared to cholecalciferol. CONCLUSIONS: In our study calcifediol showed to be as safe as cholecalciferol and more effective than cholecalciferol in order to increase vitamin D serum level after four and 12 months of supplementation when supplementation is combined with alendronate 70 mg in osteoporotic women.

Effects of alendronate and calcifediol compared to alendronate and cholecalciferol in osteoporotic patients.

BACKGROUND: Several formulations of vitamin D and alendronate are available for the treatment of osteoporosis. The objective of this study was to examine efficacy and safety of calcifediol (25(OH)D) compared to cholecalciferol (vitamin D3) and also the relationship between different formulations of alendronate and adverse reactions. METHODS: We observed a population of women diagnosed with postmenopausal osteoporosis or osteopenia treated with alendronate 70 mg weekly associated to vitamin D3 or 25(OH)D at monthly total dose of 625 µg. Data collected both at baseline (T0) and at follow-up after at least 12 months of therapy (T1) were: demographic characteristics, BMI, full medical history, lumbar T-score, femur T-score, calcium, osteocalcin, alkaline phosphatase, PTH and vitamin D blood level. RESULTS: A total of 362 patients were enrolled in the study. Alendronate 70 mg + calcifediol (A+25(OH)D) group consisted of 202 patients while 160 patients were treated with alendronate 70 mg + cholecalciferol (A+D3). In the A+25(OH)D group, we observed a significant increase in lumbar T-score value (0.26±0.35 vs. 0.13±0.3) and serum vitamin D (20.64±20.71 vs. 6.07±7.61 ng/mL) levels compared to the A+D3 group (P<0.05). The lowest incidence of gastrointestinal adverse reactions was observed among patients taking alendronate 70 mg in drinkable solution form (P<0.05). CONCLUSIONS: Alendronate 70 mg with calcifediol gives a better outcome in the treatment of osteoporosis according to lumbar T-score and vitamin D serum level observed at one-year follow-up compared to alendronate 70 mg with cholecalciferol. Both vitamin D formulations did not show to cause hypercalcemia in this study. Alendronate 70 mg in drinkable solution form is also associated with lowest incidence of gastrointestinal adverse reactions.

Bone metabolism changes during anti-TNF-alpha therapy in patients with active rheumatoid arthritis.

Osteoporosis (OP) occurs more frequently in patients with rheumatoid arthritis (RA) than in healthy individuals. Specific treatments of RA may increase susceptibility to OP, but at the same time decrease inflammatory activity, which is associated with accelerated bone loss. Treatment with TNF-alpha blockers might influence bone metabolism and prevent structural bone damage in RA, in particular at the periarticular level. Our aim was to assess the influence of anti-TNF-alpha therapy on bone metabolism in RA patients. To that end we evaluated a group of 30 RA patients [mean age 50.6 +/- 6.8 years; median disease duration 82 +/- 38 months; median disease activity score (DAS-28) 5.8 +/- 1.2: 70% of whom were positive for the rheumatoid factor IgM (>40 IU/mL)]. Patients were treated with stable therapy of prednisone (7.5 mg/day) and methotrexate (MTX = 10 mg/week). Eleven of these RA patients further received etanercept (25 mg, twice/weekly) and 10 infliximab (3 mg/kg on 0, 2, 6, and every 8 weeks thereafter). A control group included 10 RA patients with stable therapy (prednisone and MTX) and without anti-TNF-alpha therapy. All the patients fulfilled the ACR criteria for the diagnosis of adult RA and were treated for 6 months. Quantitative ultrasound (QUS) bone densitometry was performed at the metaphyses of the proximal phalanges of both hands with a DBM Sonic 1200 QUS device (IGEA, Carpi, Italy). Amplitude-dependent speed of sound (AD-SoS) was evaluated at base line and at 3 and 6 months. Bone mineral density (BMD) of the hip and lumbar spine (L1-L4) was determined by a densitometer (GE Lunar Prodigy, USA) at base line at after 6 months. Soluble bone turnover markers [osteocalcin (BGP) and deoxypyridinoline/creatinine (Dpd/Cr) ratio] were measured in all patients at the same times, using enzyme-linked immunosorbent assay tests. All data were compared using Wilcoxon signed rank test. Results were as follows: AD-SoS values were found increased by 1.3% after 6 months of treatment in the RA patients treated with anti-TNF-alpha therapy. On the contrary, the Ad-SoS levels decreased by 4.6% during the same period in the untreated RA group. BMD increased by 0.2% at lumbar spine and 0.1% at the hip in TNF-alpha-blocker-treated patients and decreased by 0.8% and 0.6% (at lumbar spine and at the hip, respectively) in RA patients without anti-TNF-alpha therapy. However, BMD variations were not significant. In RA patients treated with TNF-alpha blockers, BGP levels were found significantly increased (14.8 +/- 3.8 mg/mL vs. 22.4 +/- 4.2 mg/mL; P < 0.01) and Dpd/Cr levels were found significantly decreased (8.2 +/- 2.1 nM vs. 4.6 +/- 1.8 nM; P < 0.01) at 6 months when compared to base line values. On the contrary, there were no significant differences in the untreated RA patients concerning these latter parameters (BGP = 12.2 +/- 3.1 mg/mL vs. 10.8 +/- 2.8 mg/mL and Dpd/Cr = 8.9 +/- 2.4 nM vs. 10.2 +/- 1.8 nM, respectively). In conclusion, during 6 months of treatment of RA patients with TNF blockers, bone formation seems increased while bone resorption seems decreased. The reduced rate of OP appears to be supported by the same mechanisms involved in the decreased bone joint resorption during anti-TNF-alpha therapy, that is, the marked decrease of the proinflammatory (i.e., TNF-alpha) cytokine effects on bone metabolism.

Serum prolactin concentrations in male patients with rheumatoid arthritis.

Altered serum prolactin (PRL) levels have been reported in autoimmune diseases; however, data of serum PRL concentrations in rheumatoid arthritis (RA) are contradictory. We evaluated the PRL status in men affected by RA and the possible relationships among serum PRL levels, bone mass, and disease activity. We investigated 29 men affected by RA and 30 age- and sex-matched controls. All patients were evaluated for serum PRL levels, parameters of disease activity, and bone mineral density (BMD) at L2-L4 and the femoral neck. Serum PRL levels were found significantly higher in men with RA than in controls (p = 0.001). High serum PRL levels were significantly correlated with duration of RA and some laboratory parameters of RA disease activity. A negative correlation between femoral BMD and serum PRL levels were found (r = -0.821, p = 0.001). Male patients affected by RA showed high serum PRL levels. The serum PRL concentration was found to be increased in relation to the duration and the activity of the disease. Serum PRL levels do not seem to have any relationship with the BMD, at least in RA.

Serum osteocalcin levels in premenopausal rheumatoid arthritis patients.

The objective of this study was to assess the occurrence of generalized bone loss in rheumatoid arthritis (RA) patients and to evaluate the factors influencing bone loss, in particular, the usefulness of bone turnover markers. Twenty-five premenopausal patients (mean age, 40 x 5 years) with active RA were compared with 27 age-matched premenopausal patients with RA but without active disease and 30 age-matched healthy premenopausal controls. Serum concentrations of osteocalcin, intact parathyroid hormone (PTH), spot urine concentrations of crosslinked N-telopeptidases of type 1 collagen (NTX), and deoxypyridinoline (DPD) were detected by ELISA and radioimmunoassay. Serum osteocalcin levels were found to be significantly lower (p < 0.001) in patients with active RA compared with patients without active RA and controls. Similarly, serum intact PTH was significantly lower (p < 0.01) in patients with active RA than in patients with RA without active disease and controls. Spot urine concentrations of NTX and DPD were significantly higher (p < 0.01) in active RA patients than in patients with nonactive RA and controls. Positive correlations between osteocalcin and marker of disease activity were found to be significant (p < 0.01). There were no significant correlations between serum intact PTH, urine concentrations of NTX and DPD, and markers of inflammation. This study suggests that generalized bone loss occurs in active RA and is characterized by an evident bone resorption correlated with the high levels of inflammation.