BACKGROUND: The efficacy of bisphosphonates for osteoporotic fracture has been consistently reported in recent randomized controlled trials (RCTs) enrolling hundreds of patients. The objective of this study was to update knowledge on the efficacy of available bisphosphonates in the prevention of vertebral and non-vertebral fractures. METHODS: An approach “using systematic reviews” on PubMed and Cochrane Library was taken. Twenty-four RCTs investigating the effects of bisphosphonates for the prevention of osteoporotic fracture were included in final analysis. A pairwise meta-analysis was conducted with a random effects model. Subgroup analysis was performed according to the type of bisphosphonate. RESULTS: The use of bisphosphonate decrease the risk of overall osteoporotic fracture (odds ratio [OR] 0.62; P<0.001), vertebral fracture (OR 0.55; P<0.001) and non-vertebral fracture (OR 0.73; P<0.001). Subgroup analysis indicated that zoledronic acid showed the lowest risk reduction (OR 0.61; P<0.001) for overall osteoporotic fractures but no significance was observed for etidronate (OR 0.34; P=0.127). CONCLUSIONS: This update meta-analysis re-confirmed that bisphosphonate use can effectively reduce the risk of osteoporotic fracture. However, there is a lack of evidence regarding etidronate for the prevention of osteoporotic fracture.
Diphosphonates* ; Etidronic Acid ; Humans ; Meta-Analysis as Topic ; Osteoporosis ; Osteoporotic Fractures* ; Risk Reduction Behavior

OBJECTIVE: To assess the efficacies of once-weekly bisphosphonates on bone mineral density (BMD) gains in Korean women aged 50 years or more. METHODS: We selected 166 patients who received: alendronate 70 mg (n=48), alendronate 70 mg + cholecalciferol 2,800 IU (n=31) or risedronate 35 mg (n=87) for one year. The baseline BMD and the % changes of BMD at one-year were compared among the three medication groups. RESULTS: The menopausal status and number of women with osteoporosis was not different among the three groups, but mean age of women was significantly lower in alendronate group. Baseline BMD at L1-4 and femur neck (FN) was similar, but baseline BMD at femur total (FT) was significantly lower in alendronate group. After one-year use, the median % changes of BMD at three sites were similar among the three groups; however, the median values were highest in alendronate + cholecalciferol group (L1-4: 4.48%, 6.74%, and 4.50%; FT: 2.09%, 3.70%, and 2.31%; FN: 3.05%, 3.79%, and 2.03%). CONCLUSION: Among three once-weekly bisphosphonates, BMD gains were highest after one-year use of alendronate+cholecalciferol, although statistically not significant.
Aged ; Alendronate ; Bone Density ; Cholecalciferol ; Diphosphonates ; Etidronic Acid ; Female ; Femur ; Femur Neck ; Humans ; Osteoporosis ; Risedronate Sodium

Zebrafish was selected as model animal, and glucocorticoid dexamethasone was used as a model compound to establish a rapid and high efficient osteopenia model. Zebrafish larvae at 4 days post fertilization (dpf) were exposed to a serial concentrations of dexamethasone solutions, and 0.5% DMSO was selected as the vehicle control group. All groups were incubated in 24-well plates (28.5 degrees C) until 9 dpf. In addition, effects of 10 micromol x L(-1) dexamethasone on preventing against osteopenia induced by etidronate disodium were also investigated. Zebrafish bones at 9 dpf were stained with alizarin red. Quantitative analysis of the stained area was performed by microscopic inspection and digital imaging methods to reflect the amount of bone mineralization. Results showed that dexamethasone group at 2.5, 10 and 25 micromol x L(-1) can decrease the staining area and the staining optical density values of zebrafish head bones when compared with the vehicle control group (0.5% DMSO), which suggested that dexamethasone can significantly reduce the zebrafish mineralized bone and the bone mineral density. Results also showed that 15 and 30 microg x mL(-1) etidronate disodium can increase the mineralized matrix of zebrafish head bone and prevent against osteopenia induced by dexamethasone. In conclusion, the study indicated that zebrafish can be an idea osteopenia model induced by dexamethasone.
Animals ; Bone Density ; drug effects ; Bone Density Conservation Agents ; pharmacology ; therapeutic use ; Bone Diseases, Metabolic ; chemically induced ; prevention & control ; Calcification, Physiologic ; drug effects ; Dexamethasone ; toxicity ; Disease Models, Animal ; Etidronic Acid ; pharmacology ; therapeutic use ; Larva ; drug effects ; growth & development ; Zebrafish

BACKGROUND: Bisphosphonate is used in osteoporosis treatment to repress osteoclast activity, which then decreases levels of osteocalcin (OC). OC, a protein secreted by osteoblasts and released from the bone matrix during osteoclastic bone resorption, has been found to control blood glucose levels by increasing insulin production and sensitivity. The question addressed in this study is whether decreasing OC through bisphosphonate treatment will provoke a change in glucose homeostasis. METHODS: Eighty-four patients with osteoporosis were treated with once-weekly risedronate 35 mg and cholecalciferol 5,600 IU. We measured fasting plasma glucose (FPG), insulin, and undercarboxylated (Glu) and carboxylated (Gla) OC levels at baseline and after 16 weeks. To estimate insulin resistance (IR) and beta-cell function (B)%, homeostasis model assessment (HOMA)-IR and HOMA-B% were also calculated, respectively. RESULTS: The mean FPG level in total subjects increased significantly from 5.3 to 5.5 mmol/L, but no changes in blood glucose were noted in the 24 subjects with impaired fasting glucose. Glu and Gla OC levels declined significantly after treatment. No correlations were observed between changes in OC and changes in glucose, however. CONCLUSIONS: Bisphosphonate treatment for osteoporosis reduced OC, but this change was not associated with changes in glucose metabolism.
Blood Glucose ; Bone Matrix ; Bone Resorption ; Cholecalciferol ; Etidronic Acid ; Fasting ; Glucose ; Homeostasis ; Humans ; Insulin ; Insulin Resistance ; Osteoblasts ; Osteocalcin ; Osteoclasts ; Osteoporosis ; Plasma ; Risedronate Sodium

OBJECTIVES: Bisphosphonates (BP) are widely used in medicine for inhibiting bone resorption; however bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a major side effect of BP. To date, there have been no specific reports on the incidence of BRONJ among Koreans. This study investigated the preliminary results from a nationwide survey of BRONJ in the Departments of Oral and Maxillofacial Surgery (OMFS) at individual training hospitals. MATERIALS AND METHODS: A total of 15 OMFS departments (10 from dental schools, 4 from medical schools, and 1 from a dental hospital) participated in a multi-centric survey. This study assessed every BRONJ case diagnosed between January 2010 and December 2010. The patient age and BP type were evaluated. RESULTS: A total of 254 BRONJ cases were collected. The majority of BRONJ cases were associated with oral BP therapy, while 21.8% of the cases were associated with intravenous administration. Alendronate was the drug most frequently related to BRONJ (59.2% of cases), followed by risedronate (14.3%) and zolendronate (17.0%). The average age of BRONJ patients was 70.0+/-10.1 years, with a range of 38-88 years of age. With the number of BP patients in Korea reported to be around 600,000 in 2008, the estimated incidence of BRONJ is at least 0.04% or 1 per 2,300 BP patients. CONCLUSION: The results suggest that the estimated incidence of BRONJ in Korea is higher than the incidence of other countries. Future prospective studies should be carried out to investigate the exact epidemiological characteristics of BRONJ in Korea.
Administration, Intravenous ; Alendronate ; Bisphosphonate-Associated Osteonecrosis of the Jaw ; Data Collection ; Diphosphonates ; Etidronic Acid ; Humans ; Incidence ; Jaw ; Korea ; Osteonecrosis ; Schools, Dental ; Schools, Medical ; Surgery, Oral ; Risedronate Sodium

OBJECTIVES: Bisphosphonates (BP) are widely used in medicine for inhibiting bone resorption; however bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a major side effect of BP. To date, there have been no specific reports on the incidence of BRONJ among Koreans. This study investigated the preliminary results from a nationwide survey of BRONJ in the Departments of Oral and Maxillofacial Surgery (OMFS) at individual training hospitals. MATERIALS AND METHODS: A total of 15 OMFS departments (10 from dental schools, 4 from medical schools, and 1 from a dental hospital) participated in a multi-centric survey. This study assessed every BRONJ case diagnosed between January 2010 and December 2010. The patient age and BP type were evaluated. RESULTS: A total of 254 BRONJ cases were collected. The majority of BRONJ cases were associated with oral BP therapy, while 21.8% of the cases were associated with intravenous administration. Alendronate was the drug most frequently related to BRONJ (59.2% of cases), followed by risedronate (14.3%) and zolendronate (17.0%). The average age of BRONJ patients was 70.0+/-10.1 years, with a range of 38-88 years of age. With the number of BP patients in Korea reported to be around 600,000 in 2008, the estimated incidence of BRONJ is at least 0.04% or 1 per 2,300 BP patients. CONCLUSION: The results suggest that the estimated incidence of BRONJ in Korea is higher than the incidence of other countries. Future prospective studies should be carried out to investigate the exact epidemiological characteristics of BRONJ in Korea.
Administration, Intravenous ; Alendronate ; Bisphosphonate-Associated Osteonecrosis of the Jaw ; Data Collection ; Diphosphonates ; Etidronic Acid ; Humans ; Incidence ; Jaw ; Korea ; Osteonecrosis ; Schools, Dental ; Schools, Medical ; Surgery, Oral ; Risedronate Sodium

Bisphosphonates are the mainstay of osteoporosis treatment. Despite the fact that bisphosphonates have a relatively good safety record and are tolerated well by the majority of patients, serious adverse events have been associated with their use. A 41-year-old man had been diagnosed with osteoporosis and had taken etidronate 200 mg/day daily for 2 years due to the judgmental error. He was referred for the management of refractory bone pain and generalized muscle ache. Serum calcium, phosphate, 25-hydroxy-vitamin D (25(OH)D), and immunoreactive parathyroid hormone (iPTH) were within normal range. Plain X-ray showed multiple fractures. Whole body bone scan confirmed multiple sites of increased bone uptakes. Tetracycline-labeled bone biopsy showed typical findings of osteomalacia. He was diagnosed with iatrogenic, etidronate-induced osteomalacia. The patient received daily parathyroid hormone (PTH) injection for 18 months. PTH effectively reverses impaired bone mineralization caused by etidronate misuse. Currently, he is doing well without bone pain. Bone mineral density significantly increased, and the increased bone uptake was almost normalized after 18 months. This case seems to suggest that human PTH (1-34) therapy, possibly in association with calcium and vitamin D, is associated with important clinical improvements in patients with impaired bone mineralization due to the side effect of bisphosphonate.
Adult ; Biopsy ; Bone Density ; Calcification, Physiologic ; Calcium ; Diphosphonates ; Etidronic Acid ; Humans ; Judgment ; Muscles ; Osteomalacia ; Osteoporosis ; Parathyroid Hormone ; Reference Values ; Vitamin D

Osteoporosis is the most common metabolic bone disease that results in an increased risk of fragility fractures. Bisphosphonates are commonly used in the treatment of osteoporosis. Concerns about their association with several possible adverse effects have been raised. Here, we experienced a rare case regarding a 63-year-old female patient who had localized amnesia related to once-monthly oral risedronate. A clear cause-and-effect relationship between the treatment of risedronate and this event has not been established and the mechanism behind the adverse effect is unknown. As clinical uses of bisphosphonates continue to expand, clinicians should be aware of the rare but potential adverse effects associated with bisphosphonates including neuropsychiatric problems.
Aged ; Amnesia ; Bone Diseases, Metabolic ; Diphosphonates ; Etidronic Acid ; Female ; Humans ; Osteoporosis ; Risedronate Sodium

The importance of vitamin D for skeletal health is well known. Vitamin D deficiency causes secondary hyperparathyroidism, high bone turnover, bone loss, and osteoporotic fractures. We report a case of a 60-year-old women presenting with brown tumor in the proximal femur secondary to vitamin D deficiency and secondary hyperparathyroidism. She took calcium supplements and vitamin D3 for 1 year and half dose of risedronate was prescribed for 5 months. After 1 year, pain in the pelvis was much improved and Bone mineral density of the lumbar spine and femoral neck increased by 37% and 29%, respectively.
Bone Density ; Calcium ; Cholecalciferol ; Etidronic Acid ; Female ; Femur ; Femur Neck ; Humans ; Hyperparathyroidism ; Hyperparathyroidism, Secondary ; Middle Aged ; Osteoporosis ; Osteoporotic Fractures ; Pelvis ; Spine ; Vitamin D ; Vitamin D Deficiency ; Vitamins ; Risedronate Sodium

INTRODUCTION: The utility of the C-terminal cross-linking telopeptide test (CTX) as a method for staging Bisphosphonate-related osteonecrosis of the jaws (BRONJ) and its healing process was examined. MATERIALS AND METHODS: A total 19 patients who were diagnosed with BRONJ underwent a fasted morning CTX test, were enrolled in this study. The serum CTX values ranged from 50 to 630 pg/mL (mean 60). The risk assessment was rated according to the CTX values of the individual patient (minimal risk, > or =150 pg/mL, moderate, 100 to 150 pg/mL, high, < or =100 pg/mL). The BRONJ scores were then calculated according to the number of BRONJ lesions and their stage. The operation was done as soon as possible, regardless of BORNJ stage. RESULTS: The mean duration of bisphosphonate therapy was 4.1 years. Of the 19 patients, 15, 2 ans 2 received alendronate, risedronate and zoledronate, respecively. Of the 19 patients who underwent a sequestrectomy, saucerization and smoothing, 15 healed after the initial surgery, 1 patient healed after one more surgical procedure, 3 patients did not heal completely but showed improvement in symptoms. Therefore, 17 out of the 19 patients healed completely with complete mucosal coverage and the elimination of pain. The risk assessment using the CTX value and disease severity were not correlated (r=-0.264, P=0.275). In addition, the risk assessment using CTX value and healing after surgery were not correlated (r=-0.147, P=0.547). CONCLUSION: The serum CTX should be considered carefully by clinicians as part of overall management. Early surgical intervention is of benefit in the treatment of stage II BRONJ.
Alendronate ; Bisphosphonate-Associated Osteonecrosis of the Jaw ; Collagen Type I ; Diphosphonates ; Etidronic Acid ; Humans ; Imidazoles ; Jaw ; Jaw Diseases ; Osteonecrosis ; Peptides ; Risk Assessment ; Risedronate Sodium