risedronate (alone or in combination) on articular cartilage in experimental model of immobilized rat knee. Twenty-five adult male albino rats were divided into five groups (five rats each): control group, immobilized group, glucosamine-treated group, risedronate-treated group, and group treated by a combination of glucosamine and risedronate. The articular cartilage was obtained for histological, immunohistochemical and morphometric studies. The immobilized group showed manifestations of osteoarthritis in the form of significant decrease of articular cartilage thickness with surface erosions, shrunken chondrocytes with pyknotic nuclei and marked manifested fall of chondrocyte number. There was manifested reduction of collagen contents of the articular cartilage using Masson trichrome stain. Safranin O–Fast Green revealed low proteoglycan contents. The collagen type II was also declined. The manikin score was 7.8. Risedronate improved this manifestation slightly more than glucosamine, but combination of booth drugs caused significant improvement of the damaged articular cartilage caused by immobilization. Oral administration of glucosamine and risedronate improved the degenerative changes of rat knee articular cartilage that follow immobilization. This improvement was more remarkable when both drugs were used in combination.]]>
Administration, Oral ; Adult ; Animals ; Cartilage, Articular ; Chondrocytes ; Collagen ; Collagen Type II ; Glucosamine ; Humans ; Immobilization ; Knee ; Male ; Manikins ; Models, Theoretical ; Osteoarthritis ; Proteoglycans ; Rats ; Risedronate Sodium

OBJECTIVE: To investigate the effects of risedronate on bone marrow adipogenesis and the expression of the receptor activator of nuclear factor κB ligand (RANKL) in adipocytes in the bone marrow micro-environment. METHODS: Primary cultured rat mesenchymal stem cells (BMSCs) with or without adipogenic induction for 14 days were treated with 1, 5, 10, and 25 μmol/L risedronate. The droplets of the differentiated adipocytes were analyzed, and Western blotting was performed to detect the expression level of RANKL. Female SD rats (24-week-old) were randomly divided into sham-operated group and ovariectomy (OVX) group, and 12 weeks after the operation, the OVX rats were further divided into control group and risedronate group (2.4 μg/kg, injected subcutaneously for 3 times a week). Eight weeks later, the bone mineral density (BMD) of the rats and bone marrow histopathology of the femurs was examined to evaluate the effect of risedronate on the fat fraction in the bone marrow. RESULTS: Risdronate significantly inhibited adipogenic differentiation of rat BMSCs and suppressed RANKL expression in the adipocytes derived from the BMSCs in a concentration-dependent manner. In OVX rats, risdronate treatment significantly increased the BMD and decreased the fat content in the bone marrow. CONCLUSIONS Risdronate can effectively inhibit the adipogenic differentiation of rat BMSCs, decrease fat content in the bone marrow, and suppress the generation and function of osteoclasts by down-regulating the expression of RANKL, which can be an important mechanism underlying the therapeutic effect of risedronate against osteoporosis.
Adipocytes ; Adipogenesis ; Animals ; Bone Density ; Bone Marrow ; Female ; Ovariectomy ; RANK Ligand ; Rats ; Rats, Sprague-Dawley ; Risedronic Acid

OBJECTIVES: We compared the effectiveness of bisphosphonates combined with activated vitamin D administered for therapy of aromatase inhibitor-induced osteoporosis after a breast cancer operation and primary postmenopausal osteoporosis through propensity score matching. METHODS: Forty-eight postmenopausal patients with estrogen receptor-positive early breast cancer, who had postoperative adjuvant treatment with aromatase inhibitors and whose T-score of bone mineral density (BMD) decreased below −2.5 (AI group), and 48 patients of primary postmenopausal osteoporosis (PO group) enrolled in this retrospective observational study. They were administered monthly risedronate or minodronate, and daily alfacalcitol or eldecalcitol were combined. Their BMD (L2–4, L-BMD), serum-corrected calcium, serum phosphate, tartrate-resistant acid phosphatase 5b (TRACP-5b), bone alkaline phosphatase (BAP), estimated glomerular filtration rate, urine calcium/creatinine ratio, intact-parathyroid hormone, and 25-hydroxy vitamin D were measured before treatment and until 24 months. RESULTS: L-BMD values increased with time compared with the baseline values in each group, and there was no significant difference in the groups. Percentage value of TRACP-5b decreased rapidly after 6 months and maintained low level until 24 months in both groups. Percentage value of BAP in the AI group decreased continuously until 24 months. In contrast, the percentage change in the PO group plateaued after 6 months. CONCLUSIONS: It is suggested that monthly oral bisphosphonate combined with activated Vitamin D is an effective therapy to increase BMD in the aromatase inhibitor-induced osteoporosis after breast cancer operation. Monitoring of kidney function and concentration of Ca in blood and urine may be necessary.
Acid Phosphatase ; Alkaline Phosphatase ; Aromatase Inhibitors ; Aromatase ; Bone Density ; Breast Neoplasms ; Breast ; Calcium ; Diphosphonates ; Estrogens ; Female ; Glomerular Filtration Rate ; Humans ; Kidney ; Observational Study ; Osteoporosis ; Osteoporosis, Postmenopausal ; Propensity Score ; Retrospective Studies ; Risedronate Sodium ; Vitamin D ; Vitamins

OBJECTIVES: The purpose of this study was to investigate the demographic and clinical characteristics of patients with medication-related osteonecrosis of the jaw (MRONJ) and to elucidate factors affecting recurrence in surgical treatment. MATERIALS AND METHODS: A total of 51 patients who were diagnosed with MRONJ were analyzed according to demographic and clinical features and treatment results through a retrospective chart review from 2013 to 2017 in the Department of Oral and Maxillofacial Surgery, Korea University Anam Hospital, Seoul in Korea. RESULTS: Alendronate composed the majority of medication doses (55.6%), followed by ibandronate (20.0%), risedronate (15.6%), and zoledronate (6.7%). Forty patients (88.9%) were given oral medication, and five patients (11.1%) were intravenously treated, and the mean duration of medication use was 61.1±42.9 months. A total of 10 patients (22.2%) had a drug holiday before MRONJ-induced dental treatment lasting an average of 6.8±7.0 months. MRONJ occurred 2.7 times more in the mandible, with 41 cases (73.2%) occurring in the mandible and 15 cases (26.8%) occurring in the maxilla, and the prevalence of affected posterior parts (premolar-molar) was six times greater than that of the anterior parts (incisor-canine) (48 cases vs 8 cases, 85.7% vs 14.3%). The most common dental cause of MRONJ was tooth extraction (69.6%). Regarding recurrence, there was no statistical difference in recurrence rate according to either site or stage. However, recurrence occurred in 4 out of 34 cases (11.8%) in the primary closure group and 9 out of 20 cases (45.0%) in the secondary healing group, and there was a statistical difference with respect to closure technique. CONCLUSION: The identified risk factors in patients taking bone resorption inhibitors can aid dental clinicians in ensuring prevention and proper treatment of MRONJ.
Alendronate ; Bone Density Conservation Agents ; Holidays ; Humans ; Jaw* ; Korea ; Mandible ; Maxilla ; Osteonecrosis* ; Prevalence ; Recurrence ; Retrospective Studies ; Risedronate Sodium ; Risk Factors ; Seoul ; Surgery, Oral ; Surgical Procedures, Operative ; Tooth Extraction

OBJECTIVE: The loosening of pedicle screws (PS) is one of the frequent problems of spinal surgery in the patients with osteoporosis. Previous studies had revealed that intermittent injection of teriparatide could reduce PS loosening by improving bone mass and quality when their patients took parathyroid hormone for a considerable duration before surgery. However, although the teriparatide is usually used after spine surgery in most clinical situations, there was no report on the efficacy of teriparatide treatment started after spine surgery. The purpose of this retrospective study was to examine the efficacy of teriparatide treatment started immediately after lumbar spinal surgery to prevent pedicle screw loosening in patients with osteoporosis.METHODS: We included 84 patients with osteoporosis and degenerative lumbar disease who underwent transforaminal interbody fusion and PS fixation and received parathyroid hormone or bisphosphonate (BP) postoperatively. They were divided into teriparatide group (daily injection of 20 μg of teriparatide for 6 months, 33 patients, 172 screws) and BP group (weekly oral administration of 35 mg of risedronate, 51 patients, 262 screws). Both groups received calcium (500 mg/day) and cholecalciferol (1000 IU/day) together. The screw loosening was evaluated with simple radiographic exams at 6 and 12 months after the surgery. We counted the number of patients with PS loosening and the number of loosened PS, and compared them between the two groups. Clinical outcomes were evaluated using visual analog scale (VAS) and Oswestry disability index (ODI) preoperatively, and at 12 months after surgery.RESULTS: There was no significant difference in the age, sex, diabetes, smoking, bone mineral density, body mass index, and the number of fusion levels between the two groups. The number of PS loosening within 6 months after surgery did not show a significant difference between the teriparatide group (6.9%, 12/172) and the BP group (6.8%, 18/272). However, during 6–12 months after surgery, it was significantly lower in the teriparatide group (2.3%, 4/172) than the BP group (9.2%, 24/272) (p < 0.05). There was no significant difference in the number of patients showing PS loosening between the teriparatide and BP groups. The teriparatide group showed a significantly higher degree of improvement of the bone mineral density (T-score) than that of BP group (p < 0.05). There was no significant difference in the pre- and post-operative VAS and ODI between the groups.CONCLUSION: Our data suggest that the teriparatide treatment starting immediately after lumbar spinal fusion surgery could reduce PS loosening compared to BP.
Administration, Oral ; Body Mass Index ; Bone Density ; Calcium ; Cholecalciferol ; Humans ; Osteoporosis ; Parathyroid Hormone ; Pedicle Screws ; Retrospective Studies ; Risedronate Sodium ; Smoke ; Smoking ; Spinal Fusion ; Spine ; Teriparatide ; Visual Analog Scale

STUDY DESIGN: Retrospective case series. PURPOSE: The purpose of this study was to determine whether discontinuing teriparatide treatment and replacing it with bisphosphonate treatment maintains the volume of the fusion mass after posterolateral fusion (PLF) in women with postmenopausal osteoporosis. OVERVIEW OF LITERATURE: Clinical data support the efficacy of parathyroid hormone (PTH) for lumbar PLF. However, the use of PTH is limited to 2 years. METHODS: We treated 19 women diagnosed with osteoporosis and degenerative spondylolisthesis with teriparatide (20 µg daily subcutaneously). All patients underwent one-level instrumented PLF. Teriparatide was used during 2 months prior to surgery and more than 8 months after surgery. After discontinuing teriparatide treatment, all patients used bisphosphonate (17.5 mg risedronate weekly, oral administration). Area of the fusion mass across the transverse processes at one segment was determined on an anteroposterior radiograph at 1, 2, and 3 years after surgery. RESULTS: We followed 19 patients for 3 years. The average duration of teriparatide treatment was 11.5 months. The bone union rate was 95%. The average area of the bone fusion mass was not significantly different between the right and left sides at 1, 2, or 3 years after surgery (p>0.05). CONCLUSIONS: This study showed that replacing teriparatide treatment with bisphosphonate maintained the bone fusion mass volume after PLF in women with postmenopausal osteoporosis.
Female ; Humans ; Osteoporosis ; Osteoporosis, Postmenopausal* ; Parathyroid Hormone ; Retrospective Studies ; Risedronate Sodium ; Spine ; Spondylolisthesis ; Teriparatide*

BACKGROUND: To retrospectively assess whether the response of subtrochanteric lateral cortex (STLC) is different according to the bisphosphonate agents in terms of bone mineral density (BMD) change. METHODS: A total of 149 subjects, who had 2- to 4-year interval follow-up of BMD using dual energy X-ray absorptiometry (DXA), were included in this retrospective study divided into following 3 groups: control group (no consumption of any anti-osteoporotic drugs, n=38), alendronate group (naïve alendronate users, n=48), risedronate group (naïve risedronate users, n=63). BMD was measured at the STLC and subtrochanteric medial cortex (STMC) in each patient by drawing rectangular ROIs at the bone cortices. The percent change of BMD at the STLC were compared between the aforementioned 3 groups by using analysis of covariance model to control five independent variables of age, body mass index, percent change of STMC, hip axis length, time interval between DXA examinations. RESULTS: The least square mean values±standard deviation of the percent change of BMD in the control, alendronate, and risedronate groups were 1.46±1.50, 2.23±1.26, and 6.96±1.11, respectively. The risedronate group showed significantly higher change of BMD percentage compared with the control (adjusted P=0.012) or alendronate (adjusted P=0.016) groups. CONCLUSIONS: The percent change of BMD at the STLC in the risedronate user group was greater than the alendronate and control groups. The implication of these changes needs to be further verified.
Absorptiometry, Photon ; Alendronate ; Body Mass Index ; Bone Density* ; Femur ; Follow-Up Studies ; Hip ; Humans ; Retrospective Studies ; Risedronate Sodium

BACKGROUND: To assess the cost-effectiveness of drug therapy to prevent osteoporotic fractures in postmenopausal women with osteopenia in Korea. METHODS: A Markov cohort simulation was conducted for lifetime with a hypothetical cohort of postmenopausal women with osteopenia and without prior fractures. They were assumed to receive calcium/vitamin D supplements only or drug therapy (i.e., raloxifene or risedronate) along with calcium/vitamin D for 5 years. The Markov model includes fracture-specific and non-fracture specific health states (i.e. breast cancer and venous thromboembolism), and all-cause death. Published literature was used to determine the model parameters. Local data were used to estimate the baseline incidence rates of fracture in those with osteopenia and the costs associated with each health state. RESULTS: From a societal perspective, the estimated incremental cost-effectiveness ratios (ICERs) for the base cases that had T-scores between -2.0 and -2.4 and began drug therapy at the age of 55, 60, or 65 years were $16,472, $6,741, and -$13,982 per quality-adjusted life year (QALY) gained, respectively. Sensitivity analyses for medication compliance, risk of death following vertebral fracture, and relaxing definition of osteopenia resulted in ICERs reached to $24,227 per QALY gained. CONCLUSIONS: ICERs for the base case and sensitivity analyses remained within the World Health Organization's willingness-to-pay threshold, which is less than per-capita gross domestic product in Korea (about $25,700). Thus, we conclude that drug therapy for osteopenia would be a cost-effective intervention, and we recommend that the Korean National Health Insurance expand its coverage to include drug therapy for osteopenia.
Bone Diseases, Metabolic* ; Breast Neoplasms ; Cohort Studies ; Cost-Benefit Analysis ; Drug Therapy ; Female ; Global Health ; Gross Domestic Product ; Humans ; Incidence ; Korea ; Medication Adherence ; National Health Programs ; Osteoporotic Fractures* ; Postmenopause ; Quality-Adjusted Life Years ; Raloxifene Hydrochloride ; Risedronate Sodium

BACKGROUND: Although bisphosphonate is effective for the prevention and treatment of osteoporosis, poor medication compliance is a key-limiting factor. We determined whether alarm clock could improve compliance with weekly bisphosphonate in patients with osteoporosis, by comparing with age- and gender-matched control group. METHODS: Fifty patients with osteoporosis were recruited and participated in alarm clock group. Patients were asked to take orally weekly risedronate for 1 year, and received alarm clock to inform the time of taking oral bisphosphonate weekly. Using the propensity score matching with age and gender, 50 patients were identified from patients with osteoporosis medication. We compared the compliance with bisphosphonate using medication possession ratio (MPR) between two groups. RESULTS: Although there was no significant difference of baseline characteristics between both groups, the mean MPR (0.80±0.33) of alarm clock group was higher than that (0.56±0.34) of control group (P<0.001). CONCLUSIONS: Alarming could improve the compliance with weekly oral bisphosphonate in patients with osteoporosis.
Compliance* ; Humans ; Medication Adherence ; Osteoporosis* ; Patient Compliance ; Propensity Score ; Risedronate Sodium

BACKGROUND: N-containing bisphosphonates (BPs), such as pamidronate and risedronate, can inhibit osteoclastic function and reduce osteoclast number by inducing apoptotic cell death in osteoclasts. The aim of this study is to demonstrate the effect of pamidronate, second generation nitrogen-containing BPs and to elucidate matrix metallo-proteinases (MMPs) mRNA expression under serum starvation and/or tumor necrosis factor alpha (TNF-α) stimulation on metabolism of intervertebral disc (IVD) cells in vitro. METHODS: Firstly, to test the effect of pamidronate on IVD cells in vitro, various concentrations (10⁻¹², 10⁻¹⁰, 10⁻⁸, and 10⁻⁶ M) of pamidronate were administered to IVD cells. Then DNA and proteoglycan synthesis were measured and messenger RNA (mRNA) expressions of type I collagen, type II collagen, and aggrecan were analyzed. Secondly, to elucidate the expression of MMPs mRNA in human IVD cells under the lower serum status, IVD cells were cultivated in full serum or 1% serum. Thirdly, to elucidate the expression of MMPs mRNA in IVD cells under the stimulation of 1% serum and TNF-α (10 ng/mL) In this study, IVD cells were cultivated in three dimensional alginate bead. RESULTS: Under the lower serum culture, IVD cells in alginate beads showed upregulation of MMP 2, 3, 9, 13 mRNA. The cells in lower serum and TNF-α also demonstrated upregulation of MMP-2, 3, 9, and 13 mRNA. The cells with various doses of pamidronate and lower serum and TNF-α were reveled partial down-regulation of MMPs. CONCLUSIONS: Pamidronate, N-containing second generation BPs, was safe in metabolism of IVD in vitro maintaining chondrogenic phenotype and matrix synthesis, and down-regulated TNF-α induced MMPs expression.
Aggrecans ; Cell Death ; Collagen ; Collagen Type I ; Collagen Type II ; Diphosphonates ; DNA ; Down-Regulation ; Humans* ; In Vitro Techniques ; Intervertebral Disc* ; Matrix Metalloproteinases* ; Metabolism ; Osteoclasts ; Phenotype ; Proteoglycans ; Risedronate Sodium ; RNA, Messenger ; Starvation ; Tumor Necrosis Factor-alpha* ; Up-Regulation