-
1.
Evaluation of a Modified Pamidronate Protocol for the Treatment of Osteogenesis Imperfecta.
Palomo, T, Andrade, MC, Peters, BS, Reis, FA, Carvalhaes, JT, Glorieux, FH, Rauch, F, Lazaretti-Castro, M
Calcified tissue international. 2016;(1):42-8
Abstract
Intravenous pamidronate is widely used to treat children with osteogenesis imperfecta (OI). In a well-studied protocol ('standard protocol'), pamidronate is given at a daily dose of 1 mg per kg body weight over 4 h on 3 successive days; infusion cycles are repeated every 4 months. Here, we evaluated renal safety of a simpler protocol for intravenous pamidronate infusions (2 mg per kg body weight given in a single infusion over 2 h, repeated every 4 months; 'modified protocol'). Results of 18 patients with OI types I, III, or IV treated with the modified protocol for 12 months were compared to 18 historic controls, treated with standard protocol. In the modified protocol, mild transient post-infusion increases in serum creatinine were found during each infusion but after 12 months serum creatinine remained similar from baseline [0.40 mg/dl (SD: 0.13)] to the end of the study [0.41 mg/dl (SD: 0.11)] (P = 0.79). The two protocols led to similar changes in serum creatinine during the first pamidronate infusion [modified protocol: +2% (SD: 21%); standard protocol: -3% (SD: 8%); P = 0.32]. Areal lumbar spine bone mineral density Z-scores increased from -2.7 (SD: 1.5) to -1.8 (SD: 1.4) with the modified protocol, and from -4.1 (SD: 1.4) to -3.1 (SD: 1.1) with standard protocol (P = 0.68 for group differences in bone density Z-score changes). The modified pamidronate protocol is safe and may have similar effects on bone density as the standard pamidronate protocol. More studies are needed with longer follow-up to prove anti-fracture efficacy.
-
2.
Alfacalcidol in men with osteoporosis: a prospective, observational, 2-year trial on 214 patients.
Ringe, JD, Farahmand, P, Schacht, E
Rheumatology international. 2013;(3):637-43
Abstract
Due to pleiotropic-synergistic actions on bone, muscle, gut, brain and different other non-skeletal tissues, alfacalcidol is an interesting drug for treating osteoporosis. In studies on glucocorticoid-induced osteoporosis, men have always been treated with calcitriol or this active D-hormone prodrug, but there is no study of male patients only in the literature. The AIM-Trial (Alfacalcidol In Men) is an extension of the control group (n = 158) of our former risedronate study in male osteoporosis (Ringe et al. in Rheumatol Int 29:311-315, 2009). In that study, we treated daily those controls with prevalent vertebral fractures with 1 μg alfacalcidol + 500 mg calcium (group A) and those without prevalent vertebral fractures with 1,000 IU plain vitamin D (Vit. D) + 1,000 mg calcium (group B). Subsequently, we added an additional 56 pairs of patients to these two groups: 28 with and 28 without prevalent vertebral fractures, reaching a total of 214 cases. That means with this design, we are comparing two groups with a different risk at onset. Due to the prevalent vertebral fractures and lower average bone mineral density (BMD) values, there was a higher risk of incident fractures in group A. After 2 years, we found significantly higher increases in lumbar spine BMD (+3.2 vs. +0.8 %) and total hip BMD (+1.9 vs. -0.9 %) in group A and B, respectively. Eighteen incident falls were recorded in the alfacalcidol group and 38 in the group treated with Vit. D (p = 0.041). There were significantly lower rates of patients with new vertebral and non-vertebral fractures in group A than in group B. Back pain was significantly reduced only with alfacalcidol. Concerning the incidence of new non-vertebral fractures, we found that there was a relation to renal function in the two groups. The advantage for alfacalcidol was mainly due to a higher non-vertebral fracture-reducing potency in patients with a creatinine clearance (CrCl) below 60 ml/min (p = 0.0019). There were no serious adverse events (SAE), and the numbers of mild-to-moderate adverse events (AE) were not different between groups. Despite the higher initial fracture risk in the alfacalcidol group, 2-year treatment with this active D-hormone prodrug showed a higher therapeutic efficacy in terms of BMD, falls and fractures. One important advantage of alfacalcidol may be that it is effective even in patients with mild-to-moderate renal insufficiency.
-
3.
Effect of hormone therapy and calcitriol on serum lipid profile in postmenopausal older women: association with estrogen receptor-α genotypes.
Sai, AJ, Gallagher, JC, Fang, X
Menopause (New York, N.Y.). 2011;(10):1101-12
-
-
Free full text
-
Abstract
OBJECTIVE The aim of this study was to examine the effect of conjugated equine estrogens alone (ET), conjugated equine estrogens + medroxyprogesterone (EPT), calcitriol alone, calcitriol + EPT/ET, or placebo on serum lipid profile and analyze the interaction with estrogen receptor-α gene single nucleotide polymorphisms (ESR-α SNPs) on the response to therapy. METHODS A total of 489 postmenopausal women older than 65 years were enrolled into a 3-year double-blind, placebo-controlled clinical trial. RESULTS In both intent-to-treat and complier (>80% adherent) analysis, there was a significant increase in serum high-density lipoproteins and a significant decrease in serum low-density lipoproteins (LDLs) and the LDL/high-density lipoprotein ratio in all hormone treatment groups compared with placebo (P < 0.05). However, serum triglycerides and very low-density lipoproteins increased in the EPT and ET + calcitriol groups versus placebo (P < 0.05). ESR-α SNPs PvuII and XbaI seemed to have a significant effect on the response to treatment. Genotypes containing the p allele showed a significantly greater decrease in serum cholesterol and very low-density lipoprotein than those having the P allele in the ET + calcitriol group (P < 0.05), and those with the x allele had a significantly greater decrease in serum cholesterol in the hormone therapy + calcitriol group at the end of 3 years versus the X allele, and a greater decrease in serum LDL in alleles x versus the X in the ET + calcitriol group (P < 0.05). CONCLUSIONS ET with or without progesterone had a favorable effect on lipid profile in postmenopausal older women, and this was dependent on estrogen receptor SNPs--PvuII and XbaI. However, this interaction with ESR-α SNPs needs to be confirmed in larger studies.
-
4.
Preliminary study of etidronate for prevention of corticosteroid-induced osteoporosis caused by oral glucocorticoid therapy.
Furukawa, F, Kaminaka, C, Ikeda, T, Kanazawa, N, Yamamoto, Y, Ohta, C, Nishide, T, Tsujioka, K, Hattori, M, Uede, K, et al
Clinical and experimental dermatology. 2011;(2):165-8
Abstract
Glucocorticoids (GCs) are widely used for the treatment of various diseases, particularly in dermatology. However, there have been few reports about the outcome of treatment for GC-induced osteoporosis in patients with dermatological conditions receiving oral GCs. The present study was undertaken to prospectively evaluate the usefulness of etidronate for preventing steroid-induced osteoporosis in patients on prolonged GC therapy as routine clinical management. In total, 110 patients receiving oral GC therapy were enrolled into the study. Of these, 87 patients were evaluated (44 patients with collagen diseases, 13 patients with autoimmune bullous dermatoses, 19 patients with chronic eczema/dermatitis, 2 patients with toxicoderma/drug eruption and 9 others). Urinary deoxypyridinoline (DPD) was evaluated as a marker of bone resorption, and serum bone-specific alkaline phosphatase (BAP) as a marker of bone formation. Significant increases in urinary DPD were seen in the control group after oral GC therapy had been continued for ≥ 1 year. Treatment with etidronate suppressed this increase. When the patients were stratified according to gender, this improvement was more obvious in women. No significant difference in serum BAP level was found between the two groups. These results suggest that bisphosphonates may be useful for preventing steroid-induced osteoporosis in dermatology patients (particularly women) receiving oral GC therapy.
-
5.
Effect of alendronate on bone metabolic indices and bone mineral density in patients treated with high-dose glucocorticoid: a prospective study.
Kaji, H, Kuroki, Y, Murakawa, Y, Funakawa, I, Funasaka, Y, Kanda, F, Sugimoto, T
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2010;(9):1565-71
Abstract
SUMMARY This prospective study, in the very early phase after initiation of glucocorticoid (GC) treatment, showed that alendronate was effective in suppressing accelerated bone resorption and subsequent decrease in bone mineral density (BMD) at the lumbar spine of patients with high-dose GC treatment. INTRODUCTION How bisphosphonates affect bone metabolism and BMD of patients with high-dose GC in the early phase, especially within 1 month is unclear. METHODS We examined the prospective effects of daily 5 mg alendronate on bone metabolism and BMD in 20 patients with high-dose GC (at least 40 mg prednisolone/day) and compared them to 34 high-dose GC-treated patients without alendronate. RESULTS Serum levels of calcium decreased at day 28 in the alendronate group. Urinary calcium excretion significantly increased after day 7 in both groups. The increase in serum parathyroid hormone (PTH) level at day 7 in the control group was not observed in the alendronate group, but PTH levels increased at day 28 and month 3 in the alendronate group. As for the bone turnover markers, the serum osteocalcin level decreased in both alendronate and control groups, but serum bone-type alkaline phosphatase levels did not show significant changes. Although the urinary type I collagen cross-linked N-telopeptide (NTX) level showed significant increases on days 7 and 28 in the control group; such early increases in urinary NTX were not observed in the alendronate group. Thereafter, the urinary NTX levels fell slowly in the alendronate group significantly. BMD at the lumbar spine significantly decreased from month 1 in the control group, whereas in the alendronate group, BMD at the lumbar spine maintained almost the same level at all time points observed. CONCLUSION Alendronate was effective in suppressing bone resorption and subsequent BMD decrease at the lumbar spine in patients with high-dose GC treatment.
-
6.
Effect of community-based nutrition education intervention on calcium intake and bone mass in postmenopausal Vietnamese women.
Hien, VT, Khan, NC, Mai, le B, Lam, NT, Phuong, TM, Nhung, BT, Nhien, NV, Nakamori, M, Yamamoto, S
Public health nutrition. 2009;(5):674-9
Abstract
OBJECTIVE To examine the effect of community-based nutrition education intervention on calcium intake and bone mass in Vietnamese postmenopausal women. DESIGN A controlled trial was conducted in two groups as intervention and control. The intervention group was given nutrition education during 18 months to improve calcium intake, while the control subjects had the usual diet. Calcium intake and bone mass were evaluated every 6 months. Bone mass was assessed by speed of sound (SOS) at calcaneus, referred to as quantitative ultrasound measurement. Anthropometric indices and serum parathyroid hormone (PTH) were determined at baseline and at the end of intervention. SETTING Two rural communes of Hai Duong province located in the Red River Delta in Vietnam. SUBJECTS A total of 140 women aged 55-65 years, who were more than 5 years postmenopausal and with low calcium intake (<400 mg/d), were recruited. After 18 months of intervention, 108 women completed the study. RESULTS Calcium intake in the intervention group had increased significantly (P < 0.01) while it had no significant changes in controls. SOS values were not changed significantly in the intervention subjects while it decreased significantly by 0.5 % in the controls (P < 0.01). The intervention led to a decrease in serum PTH by 12 % (P < 0.01). In the controls, there was an increase in serum PTH by 32 % (P < 0.001). CONCLUSION Nutrition education intervention was effective in improving calcium intake and retarding bone loss in the studied subjects.
-
7.
Raloxifene slows down the progression of intima-media thickness in postmenopausal women.
Colacurci, N, Fornaro, F, Cobellis, L, De Franciscis, P, Torella, M, Sepe, E, Arciello, A, Cacciapuoti, F, Paolisso, G, Manzella, D
Menopause (New York, N.Y.). 2007;(5):879-84
Abstract
OBJECTIVE To investigate the effect of raloxifene on atherosclerosis progression in healthy postmenopausal women. DESIGN In a prospective fashion, a total of 155 healthy postmenopausal women were randomly assigned to receive raloxifene 60 mg/day or a matching placebo for 18 months. Atherosclerosis progression was evaluated by B-mode ultrasonography measuring the intima-media thickness (IMT) of the carotid arteries. Plasma levels of triglycerides, low-density lipoprotein cholesterol, soluble forms of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, E-selectin, interleukin-6, tumor necrosis factor alpha, adiponectin, and the degree of insulin resistance by the homeostatic model assessment method were also determined. RESULTS The progression slope of carotid IMT was 0.0112 mm/18 months in the raloxifene group and 0.0857 mm/18 months in the placebo group (P<0.004). Raloxifene treatment compared with placebo produced a significant decrease in plasma triglycerides (P<0.02), low-density lipoprotein cholesterol (P<0.02), soluble forms of intercellular adhesion molecule-1 (P<0.005) and vascular cell adhesion molecule-1 (P<0.04), E-selectin (P<0.02), interleukin-6 (P<0.005), tumor necrosis factor alpha (P<0.005) levels, and homeostatic model assessment index (P<0.005) and a significant increase in plasma adiponectin levels (P<0.001). Logistic regression analysis indicated that women receiving raloxifene had a lower risk of IMT progression (odds ratio=0.41; 95% CI: 0.32-0.70). CONCLUSION Raloxifene treatment, possibly through an increase in plasma adiponectin levels, may slow the progression of IMT in postmenopausal women.
-
8.
Clinical effect of bisphosphonate and vitamin D on osteoporosis: reappraisal of a multicenter double-blind clinical trial comparing etidronate and alfacalcidol.
Fujita, T, Orimo, H, Inoue, T, Kaneda, K, Sakurai, M, Morita, R, Yamamoto, K, Sugioka, Y, Inoue, A, Takaoka, K, et al
Journal of bone and mineral metabolism. 2007;(2):130-7
Abstract
As inhibitors of bone resorption, bisphosphonates and vitamin D derivatives have been extensively used for the treatment of osteoporosis in various parts of the world, but the clinical effects of these two groups of agents have rarely been compared in detail. A multicenter, prospective, double-blind controlled study was started comparing the effects of etidronate and alfacalcidol (1-alpha-hydroxycholecalciferol) in 414 patients with established osteoporosis from 36 centers. Among these patients, 135 were given 400 mg etidronate daily at bedtime for 2 weeks followed by 10 weeks off treatment, and this cycle was repeated four times along with a placebo indistinguishable from the alfacalcidol capsule daily throughout the 48 weeks of study (Group A, High Dose Etidronate Group). In 133 patients, 200 mg etidronate was used instead of 400 mg (Group B, Low Dose Etidronate Group). In 138 patients, 1 microg alfacalcidol was given daily throughout the 48-week study period along with a placebo indistinguishable from the etidronate tablet in four separate periods of 2 weeks (Group C, Control Group). Dual-energy X-ray absorptiometry of the lumbar spine (L2-L4) was performed before the beginning of the study and every 12 weeks thereafter. Changes in spinal deformity were also assessed based on the lateral thoracic and lumbar spine X-ray films taken before and after the study. The lumbar spine bone mineral density (BMD) changes were +3.4% +/- 0.6% (mean +/- SEM) in Group A, +2.4% +/- 0.5% in Group B, and -0.5% +/- 0.4% in Group C, the former two being significantly higher than the last. New occurrence of spinal compression fracture was also significantly reduced in Group A compared to Group C. In patients without previous fracture at entry, incident fracture was 10.2% in Group C, but 0% in Groups A and B. In patients with prevalent fracture at entry, corresponding figures were 21.5% (Group C), 12.0% (Group A), and 13.2% (Group B), respectively. Alfacalcidol maintained lumbar spine BMD, preventing a decrease for 48 weeks, and etidronate significantly increased it further, demonstrating its usefulness in the treatment of established osteoporosis.
-
9.
Longitudinal evaluation of serum leptin and bone mineral density in early postmenopausal women.
Di Carlo, C, Tommaselli, GA, Di Spiezio Sardo, A, Sammartino, A, Attianese, W, Gargano, V, Bifulco, G, Nappi, C
Menopause (New York, N.Y.). 2007;(3 Pt 1):450-4
Abstract
OBJECTIVE To evaluate total and site-specific bone mineral density (BMD) and serum leptin levels in postmenopausal women treated with a calcium supplement and in postmenopausal women receiving estrogen plus progestin therapy. DESIGN Forty-four women were randomized to receive either calcium supplementation (group A, n = 22) or transdermal 17beta-estradiol at a dose of 50 mug/day in a continuous regimen and nomegestrol at a dose of 5 mg/day for 12 days per month in a sequential regimen (group B, n = 22). All women underwent dual-energy x-ray absorptiometry determination of BMD and blood sampling in the morning at the beginning of the study and after 12 months. Leptin was determined by radioimmunoassay in all samples. RESULTS After 12 months, serum leptin levels were significantly higher in group A (control) in comparison with group B and baseline values, whereas both total and pelvic BMDs were significantly lower in group A in comparison with group B and baseline values. At baseline, a significant correlation was found between leptin levels, body mass index, and total-body BMD. After 12 months, leptin was still correlated to body mass index in both groups, but the association with BMD was lost. CONCLUSIONS This study confirms previous evidence of a significant correlation between serum leptin and BMD in early postmenopausal women. Furthermore, this correlation is lost over time during the progression of the postmenopausal period, independently from the administration of estrogen-progestin therapy. Further studies and longer follow-up periods are needed to better understand theses issues.
-
10.
Biphosphonate-associated osteonecrosis can be controlled by nonsurgical management.
Montebugnoli, L, Felicetti, L, Gissi, DB, Pizzigallo, A, Pelliccioni, GA, Marchetti, C
Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics. 2007;(4):473-7
Abstract
Sixteen patients with jaw biphosphonate-osteonecrosis and with exposed bone areas were subdivided into 2 treatment groups. The first group (7 patients) underwent superficial or radical surgical therapy, while the second (9 patients) underwent antibiotic treatment. A slight reduction of the necrotic areas was observed in 5 of 7 patients in the first group, whereas no change was observed in the remaining 2 patients at 22- and 24-month follow-up. A slight reduction of the necrotic areas was observed in 7 of 9 patients in the second group, whereas no change was observed in the remaining 2 patients at 5- and 24-month follow-up. The statistical analysis showed that the treatment regimen did not significantly influence the dimensional change in the exposed bone. The preliminary results seem to suggest that biphosphonate-associated osteonecrosis can be well controlled by a nonsurgical protocol consisting in long-term administration of antibiotics.