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Clinical characteristics associated with bone mineral density improvement after 1-year alendronate/vitamin d3 or calcitriol treatment: Exploratory results from a phase 3, randomized, controlled trial on postmenopausal osteoporotic women in China.
Liao, EY, Zhang, ZL, Xia, WB, Lin, H, Cheng, Q, Wang, L, Hao, YQ, Chen, DC, Tang, H, Peng, YD, et al
Medicine. 2018;(31):e11694
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Baseline and on-treatment characteristics, including age, obesity, calcium intake, and bone turnover markers, may predict the bone mineral density (BMD) response in women with postmenopausal osteoporosis (PMO) to 1 to 2 years of antiresorptive therapy and/or vitamin D supplementation. This study aimed to explore clinical characteristics associated with 12-month BMD improvement in Chinese women with postmenopausal osteoporosis (PMO).In this post hoc analysis of a previous phase 3 multicenter, randomized controlled trial, Chinese PMO women who were treated with once weekly alendronate 70 mg/vitamin D3 5600 IU (ALN/D5600) or once daily calcitriol 0.25 mcg, and had measurements of 1-year lumbar spine BMD (LS-BMD) and on-treatment bone turnover markers (BTMs) were included in the analysis.In Chinese PMO patients on ALN/D5600, 1-year LS-BMD change was negatively correlated with age (β = -0.00084, P < .01), dietary calcium (β = -0.0017, P = .07), and procollagen type 1 N-terminal propeptide (P1NP) change at month 6 (β = -0.000469, P = .0016), but positively with body mass index (BMI) (β = 0.00128, P = .08); baseline P1NP above the median was associated with a significantly greater BMD percentage change at the lumbar spine (P = .02) and the total hip (P = .0001). In the calcitriol group, a significant 1-year LS-BMD increase was associated with BMI (β = 0.0023, P = .02), baseline P1NP (β = 0.00035, P = .0067), history of prior vertebral fracture(s) (β = 0.034, P < .0001) and baseline serum 25(OH)D level (β = -0.00083, P = .02).The presented findings from Chinese postmenopausal osteoporotic women suggested clinically meaningful baseline and on-treatment characteristics predicting BMD improvement after 1 year of ALN/D5600 treatment, which differed from calcitriol treatment with baseline identifiable associations. The study remained exploratory and further accumulation of evidence is needed.
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Open-label study of treatment with alendronate sodium plus vitamin D in men and women with osteoporosis in Thailand.
Songpatanasilp, T, Rojanasthien, S, Sugkraroek, P, Ongphiphadhanakul, B, Robert, L, Robert, CS, Luevitoonvechkij, S, Santora, AC
BMC musculoskeletal disorders. 2018;(1):392
Abstract
BACKGROUND It is generally believed that Thai people do not suffer from hypovitaminosis D because there is abundant sunlight throughout the year, and that taking vitamin D supplements could result in abnormally high levels of vitamin D. This is a Thai FDA-driven study to investigate this risk over a period of 26 weeks of taking alendronate sodium/vitamin D3 combination tablets. METHODS Osteoporosis patients in Thailand were recruited to a multicenter, open-label, 6-month trial of oral alendronate sodium 70 mg/vitamin D3 5600 IU. Patients received study medication once a week for 26 weeks. Serum 25-hydroxyvitamin D (25(OH)D) and Beta-CrossLaps (β-CTx) levels were measured at baseline and 26 weeks. The primary endpoint was the proportion of patients with 25(OH)D ≥ 50 ng/mL at week 26; it was hypothesized that 26 weeks' treatment would not result in 25(OH)D serum levels ≥ 50 ng/mL in > 7% of osteoporosis patients. RESULTS One hundred ninety-eight patients were recruited. At baseline, 67.2% of the patients had 25(OH)D < 30 ng/mL; this declined to 34.4% by week 26. The mean 25(OH)D level improved from 27.8 ng/mL at baseline to 33.6 ng/mL at week 26. Five patients (2.69% of the full analysis set) had 25(OH)D levels ≥ 50 ng/mL at 26 weeks. The highest 25(OH)D level, 64.3 ng/mL, was observed in a patient whose baseline level was 102.2 ng/mL. The majority (62.9%) of the patients had optimal 25(OH)D levels (30-50 ng/mL). β-CTx levels were reduced by 57.7% after 26 weeks' treatment. No clinically significant cases of hypercalcemia which could be associated with hypervitaminosis D were identified during physical examination, in vital signs, or in laboratory results. Overall, 73 patients (36.9%) reported at least one adverse event (AE), with 13 (6.6%) reporting drug-related AEs. Four patients discontinued due to AEs, two of which were drug-related. Serious AEs were reported for four patients, of which one was considered drug-related. CONCLUSIONS Oral alendronate sodium 70 mg plus vitamin D3 5600 IU once weekly had an acceptable safety profile in this study, and increased serum 25(OH)D and reduced β-CTx levels in osteoporosis patients. This treatment improved 25(OH)D levels, without causing abnormally high levels, after 26 weeks' treatment. TRIAL REGISTRATION Clinical Trials.gov NCT01437111 , Registered September 19, 2011.
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Overlapping and continued alendronate or raloxifene administration in patients on teriparatide: effects on areal and volumetric bone mineral density--the CONFORS Study.
Muschitz, C, Kocijan, R, Fahrleitner-Pammer, A, Pavo, I, Haschka, J, Schima, W, Kapiotis, S, Resch, H
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2014;(8):1777-85
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Nine month teriparatide (TPTD) monotherapy followed by co-administration of raloxifene (RAL) or alendronate (ALN) for another nine 9 months resulted in incremental bone mineral density (BMD) increase. The aim of this study was to investigate the effects of continued antiresorptive treatments for 12 months in the extension phase. Postmenopausal women (n = 125) with severe osteoporosis on ongoing TPTD treatment for 9 months were randomized into three open-label groups for another 9 months: ALN (70 mg/week, n = 41), RAL (60 mg/d, n = 37) in addition to TPTD or no additional medication (n = 47) except Ca and vitamin D. After discontinuation of TPTD the respective antiresorptives were continued for a further 12 months, while patients in the TPTD monotherapy group received Ca and vitamin D. Amino-terminal propeptide of type I procollagen (P1NP) and cross-linked C-telopeptide (CTX), areal and volumetric BMD at the lumbar spine (LS) and hip were assessed. ALN resulted in continued BMD increase in LS (4.3 ± 1.5%; mean ± SD), femoral neck (4.2 ± 1.6%) and total hip (4 ± 1.6%; p < 0.001 for all), while RAL was only effective at the LS (2.4 ± 1.7%, p < 0.001) but no changes at the femoral neck (0.4 ± 1.4%) or total hip (-0.8 ± 1.5%) were observed. Cortical bone only increased in the ALN group (femoral neck 6.7 ± 2.7% and -1.3 ± 2.5%; total hip 13.8 ± 2.9% and -2.3 ± 2.5% for ALN and RAL, p < 0.001 for all; respectively). Analyzing the entire 30 months of therapy, the ALN group revealed the largest BMD increase in all regions. Our results suggest that the addition of ALN to ongoing TPTD and continuing ALN after TPTD was stopped may be beneficial for patients in terms of areal and volumetric BMD increase. Further research is warranted to determine the optimal timing of the initiation of the combination treatment, the respective antiresorptive medication and the potential benefit of this BMD increase regarding fracture prevention.
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Successful treatment of calcific uraemic arteriolopathy with bisphosphonates.
Torregrosa, JV, Durán, CE, Barros, X, Blasco, M, Arias, M, Cases, A, Campistol, JM
Nefrologia : publicacion oficial de la Sociedad Espanola Nefrologia. 2012;(3):329-34
Abstract
BACKGROUND AND OBJECTIVES Calcific uraemic arteriolopathy (CUA), also known as calciphylaxis, is a rare but life-threatening condition that almost exclusively affects patients with chronic kidney disease. Several therapies have been employed to treat this disease but with irregular results. We report a prospective case series of eight patients diagnosed with CUA in our unit between 2002 and 2010. MATERIAL AND METHOD The series consisted of eight patients with CUA (including 4 men, 5 dialysis patients and 3 with functioning allografts) who were treated with bisphosphonates. The diagnosis was by clinical suspicion and a confirmatory biopsy. Five patients had a previous history of high calcium-phosphorus product, 6 had a history of high parathyroid hormone levels (>800pg/ml), 4 had undergone parathyroidectomy, 5 had a history of high cumulative doses of steroids, and 6 patients were under dicoumarin treatment. None of the patients were obese or had diabetes mellitus. RESULTS In all patients, progression of skin lesions stopped between 2 to 4 weeks after starting bisphosphonate therapy, with no changes in blood levels of calcium and phosphate. Improvement in pain and lesions was faster in patients receiving intravenous ibandronate. All of these patients remained on bisphosphonate treatment for at least 6 months until the wounds healed completely. No recurrences have been observed after follow-up periods between 1 and 9 years. Renal function remained stable in transplant recipients. The treatment was well tolerated and no adverse effects were observed. CONCLUSIONS Bisphosphonates could be a new and attractive alternative to treat CUA.
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Low acceptance of treatment in the elderly for the secondary prevention of osteoporotic fracture in the acute rehabilitation setting.
Berry, SD, Misra, D, Hannan, MT, Kiel, DP
Aging clinical and experimental research. 2010;(3):231-7
Abstract
BACKGROUND AND AIMS Given the high risk of subsequent fracture among elderly persons with fracture, it is important to initiate secondary treatment for osteoporosis. Acute rehabilitation centers may offer a unique opportunity to introduce treatment. Therefore, we evaluated willingness-to-participate and compliance with evidence-based interventions for the secondary prevention of osteoporotic fracture in a non-randomized study conducted in the acute rehabilitation setting. We also described differences in baseline characteristics between study participants and non-participants. METHODS All consecutive, community dwelling admissions to an acute rehabilitation unit (Boston, MA) with the diagnosis of fracture were screened for enrollment. Eligible subjects were offered a free, 6-month supply of alendronate/cholecalciferol (70 mg/2800 IU weekly), calcium and vitamin D supplements, and fall prevention strategies. Six-month compliance (> or =75% consumption of medication or supplement) with the interventions was determined at a home visit. RESULTS Among 62 eligible subjects, 25 agreed to participate. Non-participants were older than participants (86 vs 80 yrs, p<0.01). There was no significant difference between other characteristics of participants and non-participants including sex, weight, type of fracture, cognitive status, and functional status. The most common reason for non-participation was reluctance to take another medication. Among participants, only 52% were compliant with alendronate and 58% were compliant with calcium and vitamin D supplementation at 6 months. CONCLUSIONS Willingness- to-participate and compliance with secondary prevention strategies for osteoporosis was low in the acute rehabilitation setting, even when medications were provided free of cost. Educating individuals with fracture and their families on the consequences and treatment of osteoporosis may help to decrease the risk of sustaining a second fracture by accepting secondary preventive measures.
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Additional beneficial effects of recombinant growth hormone in alendronate-treated patients with idiopathic osteoporosis.
Lopes, RF, Coeli, CM, Vaisman, M, de Farias, ML
Endocrine journal. 2009;(7):851-8
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In order to study the benefit of adding recombinant human growth hormone (rhGH) to antiresorptive therapy, six patients with idiopathic osteoporosis (IO) receiving alendronate plus calcium and vitamin D were started on daily subcutaneous injections of rhGH 2.0 IU for one year. Fasting morning urine and serum samples were collected for N telopeptide of type-1 collagen (NTX), serum bone-specific alkaline phosphatase (BSAP) and insulin-like growth factor 1 (IGF-1) during the study. Bone mineral density (BMD) was determined by dual-energy x-ray absorptiometry at baseline and 01 year. The effect of rhGH was evaluated comparing the percentage changes in BMD during the last year on ALN with the results obtained with the combined therapy. Serum IGF-1 increased in all patients but variations were not significant (p=0.266). Serum BSAP did not significantly change (p=0.078) but median NTX increased at 45 days from 12.3 to 19.8 nMBCE/mMCr (p=0.012) and tended to return to baseline values at 12 months (15.2 nMBCE/mMCr). Comparing with isolated ALN therapy, a beneficial effect on bone density was observed in 2/3 of the patients at lumbar spine, and percentage change (median and quartiles) varied from -0.65% (-2.33 and 2.23) on ALN to 0.70% (-0.35 and 3.03) on ALN+GH. Although no bone gain occurred at the femoral neck, our data point to a positive effect of rhGH in patients with idiopathic osteoporosis.
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Alendronate in combination with calcium and vitamin D prevents bone loss after orthotopic liver transplantation: a prospective single-center study.
Millonig, G, Graziadei, IW, Eichler, D, Pfeiffer, KP, Finkenstedt, G, Muehllechner, P, Koenigsrainer, A, Margreiter, R, Vogel, W
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2005;(8):960-6
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Bone loss is a common complication in patients before and after liver transplantation (LT). The aim of this study was to investigate the efficacy of prophylactic treatment with bisphosphonates after LT in preventing progressive bone loss in LT patients. We included 136 patients with end-stage liver diseases awaiting LT. Bone mineral density (BMD) (by dual X-ray absorptiometry) and markers of bone metabolism were determined before, and 4, 12, 24, 36, and 48 months after LT. All patients received vitamin D and calcium supplementation before and after LT, those with osteopenia or osteoporosis prior to LT were additionally treated with alendronate following LT. Decreased BMD was seen in a high percentage of patients undergoing LT (osteopenia 48.5%, osteoporosis 23.5%). Reduced BMD before LT was not related to gender, underlying liver disease, or Child-Turcotte-Pugh classification. Body mass index (BMI) prior to LT, however, correlated significantly with the fracture risk. Alendronate prevented the ubiquitously observed bone loss after LT in patients with osteoporosis and osteopenia and, in addition, led to an increase in BMD in patients with osteoporosis within 24 months after LT. In conclusion, our study suggests that alendronate is efficacious in preventing the natural course of bone loss associated with LT.
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Prevention of bone loss in paraplegics over 2 years with alendronate.
Zehnder, Y, Risi, S, Michel, D, Knecht, H, Perrelet, R, Kraenzlin, M, Zäch, GA, Lippuner, K
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2004;(7):1067-74
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UNLABELLED To assess the effects of long-term treatment of bone loss with alendronate in a group of paraplegic men, 55 patients were evaluated in a prospective randomized controlled open label study that was 2 years in duration comparing alendronate and calcium with calcium alone. Bone loss was stopped at all cortical and trabecular infralesional sites (distal tibial epiphysis, tibial diaphysis, total hip) with alendronate 10 mg daily. INTRODUCTION Bone loss after spinal cord injury (SCI) leads to increased fracture risk in the lower limbs of paraplegics. The aim of this study was to document long-term treatment of bone loss with alendronate in a group of paraplegic men with complete motor lesion after SCI. MATERIALS AND METHODS Sixty-five men with complete motor post-traumatic medullary lesion between T1 and L2 with total motor and sensory loss (Frankel classification, stage A) or with total motor and partial sensory loss (Frankel classification, stage B) after SCI were included in this prospective randomized controlled open label study that was 2 years in duration. The patients were randomized to either the treatment group with alendronate 10 mg daily and elemental calcium 500 mg daily or to the control group with elemental calcium 500 mg daily alone. The primary endpoint was defined as the effect over 24 months of alendronate and calcium compared with calcium alone on the BMD values at the distal tibial epiphysis (as a surrogate for trabecular bone in the paralyzed zone). The secondary endpoints were changes in BMD at supra- and infralesional sites of measurement. Biochemical markers of bone turnover were assessed. RESULTS Fifty-five subjects, 0.1-29.5 years post-SCI, completed the study over 24 months. BMD at the distal tibial epiphysis significantly decreased from baseline in the calcium group (-10.8 +/- 2.7% at 24 months, p < 0.001), whereas it remained stable in the alendronate plus calcium group (-2.0 +/- 2.9% at 24 months, p = not significant versus baseline), leading to a significant intergroup difference over time (p = 0.017). At the tibial diaphysis, similar significant results were observed. At the ultradistal radius and the radial shaft, BMD did not change significantly from baseline in either treatment group. At the total hip, BMD decreased significantly in the calcium group (-4.1 +/- 1.6%, p = 0.038) but remained stable in the alendronate plus calcium group (+0.43 +/- 1.2%), with a significant intergroup difference (p = 0.037). At the lumbar spine, BMD increased significantly (p < 0.0001) from baseline in both groups. Biochemical markers of bone resorption were significantly decreased with alendronate versus baseline and control. Alendronate and calcium were generally safe and well tolerated. CONCLUSIONS In paraplegic men, SCI bone loss was stopped at all measured cortical and trabecular infralesional sites over 24 months with alendronate 10 mg daily.
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Determinants of one-year response of lumbar bone mineral density to alendronate treatment in elderly Japanese women with osteoporosis.
Iwamoto, J, Takeda, T, Sato, Y, Uzawa, M
Yonsei medical journal. 2004;(4):676-82
Abstract
The purpose of this study was to determine factors that could predict the one-year response of the lumbar bone mineral density (BMD) to alendronate treatment in elderly Japanese women with osteoporosis. Eighty-five postmenopausal women with osteoporosis, all of whom were between 55-88 years of age, were treated with alendronate (5 mg daily) for 12 months. Serum calcium, phosphorus, and alkaline phosphatase (ALP) and urinary NTX levels were measured at the baseline and 6 months, and lumbar (L1-L4) BMD was measured by dual energy X-ray absorptiometry at the baseline and 12 months. Multiple regression analysis was used to determine factors that were correlated with the percent change in lumbar BMD at 12 months. Lumbar BMD increased by 8.1 % at 12 months with a reduction in the urinary NTX level by 51.0 % at 6 months. Baseline lumbar BMD (R2=0.226, p < 0.0001) and percent changes in serum ALP and urinary NTX levels (R2=0.044, p < 0.05 and R2=0.103, p < 0.001, respectively) had a negative correlation with the percent change in lumbar BMD at month 12, while the baseline number of prevalent vertebral fractures (R2=0.163, p < 0.001), serum ALP level, and urinary NTX level (R2=0.074, p < 0.05 and R2=0.160, p < 0.001, respectively) had a positive correlation with it. However, baseline age, height, body weight, body mass index, years since menopause, serum calcium and phosphorus levels, and percent changes in serum calcium and phosphorus levels at 6 months did not have any significant correlation with the percent change in lumbar BMD at 12 months. These results suggest that lumbar BMD was more responsive to one-year of alendronate treatment in elderly osteoporotic Japanese women with lower lumbar BMD, more prevalent vertebral fractures, and higher bone turnover, who showed a greater decrease in bone turnover at 6 months, regardless of age, years since menopause, and physique. Alendronate may be efficacious in elderly Japanese women with evident osteoporosis that is associated with high bone turnover, and the percent changes in serum ALP and urinary NTX levels at 6 months could predict the one-year response of lumbar BMD to alendronate treatment.
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Differential effects of teriparatide on BMD after treatment with raloxifene or alendronate.
Ettinger, B, San Martin, J, Crans, G, Pavo, I
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2004;(5):745-51
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UNLABELLED We investigated the effects of 18 months of treatment with teriparatide in patients previously treated with long-term antiresorptive therapy using bone turnover markers and bone densitometry. Previous raloxifene treatment allowed for teriparatide-induced early bone marker and BMD increases comparable with previously published results for treatment-näive patients. Conversely, previous alendronate treatment reduced the bone marker and BMD response. INTRODUCTION Teriparatide [rhPTH(1-34)] has been shown to increase BMD and reduce the risk of fracture in postmenopausal women with osteoporosis. Our objective was to investigate the skeletal effects of 18 months of treatment with teriparatide in women whose osteoporosis was previously treated with either alendronate or raloxifene. MATERIALS AND METHODS Daily subcutaneous injections of 20 microg teriparatide were administered for 18 months to 59 postmenopausal women, 60-87 years of age, with BMD T-scores ≤ -2.0 who had previously received either alendronate (ALN) or raloxifene (RLX) therapy for 18-36 months. All patients received daily calcium (1000 mg) and vitamin D (400 IU) supplementation. The primary study outcome was change in lumbar spine BMD measured by DXA. Secondary outcomes included changes in bone turnover markers, total hip BMD, and safety. RESULTS Median baseline bone turnover marker levels in prior ALN patients were about one-half those of prior RLX patients. During teriparatide treatment, bone markers in prior ALN patients increased later and peaked at about one-third lower levels compared with prior RLX patients. During the first 6 months, there were statistically significant (p < 0.05) group differences in BMD change at the hip (prior ALN -1.8% versus prior RLX +0.5%) and at the spine (prior ALN +0.5% versus prior RLX +5.2%). The positive slopes in hip and lumbar spine BMD were similar in both groups between 6 and 18 months. After 18 months, mean lumbar spine BMD increased 10.2% in prior RLX compared with 4.1% in prior ALN (p < 0.05) patients. Furthermore, at 18 months, mean total hip BMD had significantly increased (1.8%, p < 0.05) in prior RLX patients but was not different from baseline in prior ALN patients. CONCLUSIONS Teriparatide treatment stimulates bone turnover in patients pretreated with both RLX and ALN. Prior treatment with RLX allows for the expected teriparatide-induced BMD increases comparable with those previously reported for treatment-näive patients. In contrast, prior treatment with ALN prevents increases in BMD, particularly in the first 6 months.