risedronic-acid and Disease-Progression

Paget's disease of bone, the second most common metabolic bone disease in the United States, is characterized by localized areas of excessive bone resorption coupled with accelerated bone formation, resulting in new bone that is less structurally organized and is weaker than normal bone. Complications of Paget's disease can include bone pain, osteoarthritis, skeletal deformity, hearing loss, and fractures. The objective of this review is to provide a comprehensive overview of current standards of treatment in Paget's disease.. A review of literature from 1974 to 2007 was performed on topics such as epidemiology, etiology, treatment of Paget's disease of bone, and bisphosphonates.. Paget's disease affects an estimated 2-7% of persons of age 55 years or older in North America and western Europe. Antiresorptive treatment with bisphosphonates is the standard treatment, but there may be limitations to oral therapy. Intravenous pamidronate is efficacious and has long been available, but its use is hindered by an impractical recommended dosing regimen of 30 mg IV over 4 h for three consecutive days. In two identical, double-blind, 6-month trials, 96% of patients treated with a one-time intravenous treatment of zoledronic acid 5 mg achieved therapeutic response, compared with 74% treated with 60 days of daily oral treatment with risedronate 30 mg (p < 0.001). One limitation of this review is that historical data are not reviewed in the same level of detail as newer treatments, because recent advances in pharmacotherapy of Paget's disease have reduced the clinical utility of the older drugs.. The etiology of Paget's disease is unclear, but some evidence suggests genetic and viral components. Bisphosphonates restore normal bone turnover and relieve bone pain, but oral formulations may be limited by complicated dosing regimens and poor gastrointestinal absorption. The bisphosphonate, zoledronic acid is administered as a single intravenous infusion and offers antiresorptive efficacy and longer-lasting remission.

Topics: Aged; Bone Density Conservation Agents; Diphosphonates; Disease Progression; Etidronic Acid; Humans; Imidazoles; Middle Aged; Osteitis Deformans; Pamidronate; Risedronic Acid; Risk Factors; Treatment Outcome; Zoledronic Acid

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.. 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.. 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.. Bisphosphonates could be a new and attractive alternative to treat CUA.

Topics: Aged; Alendronate; Alkaline Phosphatase; Arterioles; Calciphylaxis; Calcium; Comorbidity; Diphosphonates; Disease Progression; Etidronic Acid; Female; Humans; Hyperparathyroidism, Secondary; Ibandronic Acid; Kidney Transplantation; Male; Middle Aged; Parathyroid Hormone; Parathyroidectomy; Phosphates; Prospective Studies; Renal Dialysis; Risedronic Acid; Skin; Uremia

This multicentre, randomised, open label, phase II/III study aimed to investigate the potential benefit of adding risedronate (R) to docetaxel (D) in patients with metastatic Castration Resistant Prostate Cancer (CRPC).. CRPC patients with bone metastasis were randomly assigned to receive D 75 mg/m(2) every 3 weeks and prednisone as first line chemotherapy, with or without R 30 mg oral once daily. The primary end-point was time to progression (TTP). A composite end-point of objective progression by RECIST criteria, PSA progression, or pain progression, whichever occurred first, was applied. The study had 80% power to detect an improvement of 30% in median TTP in the DR group (two-sided α=0.05).. Five hundred and ninety-two men (301 D versus 291 DR) were randomised. TTP was 7.4 [D] versus 6.5 [DR] months (p=0.75). PSA and pain response rates were similar, 66.3% [D] versus 65.9% [DR] and 27.9% [D] versus 31.2% [DR], respectively. Median overall survival (OS) was 18.4 [D] versus 19.2 [DR] months (p=0.33). There were no differences in toxicity.. The addition of the third generation bisphosphonate, risedronate, in the setting of effective first line docetaxel based chemotherapy did not increase efficacy, as indicated by the lack of improvement in TTP, OS, PSA- and pain response.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Bone Density Conservation Agents; Bone Neoplasms; Castration; Disease Progression; Docetaxel; Etidronic Acid; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Netherlands; Norway; Pain; Prednisone; Proportional Hazards Models; Prostate-Specific Antigen; Prostatic Neoplasms; Risedronic Acid; Risk Assessment; Risk Factors; Taxoids; Time Factors; Treatment Outcome

Little is known about the natural history of knee osteoarthritis (OA). We sought to identify common patterns of joint space narrowing (JSN) in well-characterized knee OA patients in the placebo arm of a 2-year international study.. We performed secondary data analyses of 622 adults ages 39-80 years in North America (n = 310) and Europe (n = 312) with symptomatic knee OA. Fluoroscopically positioned semiflexed anteroposterior radiographs were obtained at 0, 12, and 24 months. Group-based trajectory modeling was used to identify distinctive groups of individuals with similar trajectories of JSN, taking into account sex, age, and body mass index.. Seven groups were identified. Four exhibited joint space width (JSW) stability over 2 years representing the most common trajectory (71%), which was unrelated to initial JSW. Atypical courses included slow, rapid, and moderate progressors; most had significant JSN at study entry. Slow progressors (20%) had a mean JSN of 0.2 mm over 2 years. Only 2% of the sample demonstrated rapid JSN (2.1 mm), while 7% had JSN of 0.7 mm. Rapid progressors tended to be men, while slow and moderate progressors were older and heavier.. Most (70%) people with OA demonstrated no significant JSN over 2 years; 20% showed slow progression, 7% had moderate, and 2% had rapid JSN. Progressors tended to have less JSW at study entry and were older and heavier; rapid progressors were more likely to be men. Understanding common patterns of the course of knee OA may offer new opportunities to target those at greatest risk of disability.

Topics: Adult; Aged; Aged, 80 and over; Bone Density Conservation Agents; Disability Evaluation; Disease Progression; Etidronic Acid; Europe; Female; Humans; Knee Joint; Male; Middle Aged; North America; Osteoarthritis, Knee; Radiography; Risedronic Acid; Severity of Illness Index; Time Factors

To investigate whether early changes in biochemical markers of bone (NTX-I) and cartilage (CTX-II [C-terminal crosslinking telopeptide of type II collagen]) degradation are associated with radiological progression in patients with knee osteoarthritis (OA) receiving risedronate.. Two thousand four hundred and eighty three patients with medial compartment knee OA were randomized in two 24-month studies in North America (NA) and European Union (EU). Studies evaluated risedronate 5 mg/day, 35 mg/week (EU), 50 mg/week (NA), and 15 mg/day (NA and EU), compared to placebo in reducing signs and symptoms and in slowing radiographic progression. One thousand eight hundred and eighty five patients from the pooled EU and NA studies with available NTX-I/CTX-II at both baseline and 6 months and radiographs at baseline and at 24 months were analyzed.. Risedronate produced a dose-dependent reduction of NTX-I and CTX-II observed at 6 months which continued up to 24 months. Patients who had CTX-II levels returned to low levels (<150 ng/mmol creatinine) at 6 months had a lower risk of radiographic progression at 24 months than patients whose CTX-II levels were increased both at baseline and 6 months [odds-ratio (95% confidence interval): 0.57 (0.39-0.85) after adjustment for demographics and joint space width]. The lowest risk of progression was observed in patients who had low CTX-II levels both at baseline and at 6 months [odds-ratio 0.36 (0.21-0.63)]. No significant association between NTX-I levels and radiological progression was observed.. CTX-II decreased with risedronate in patients with knee OA and levels reached after 6 months were associated with radiological progression at 24 months. Monitoring a marker of cartilage degradation 6 months after initiating treatment may be instructive in identifying patients with low progression.

Topics: Aged; Biomarkers; Bone Density Conservation Agents; Bone Resorption; Cartilage, Articular; Collagen Type I; Disease Progression; Dose-Response Relationship, Drug; Double-Blind Method; Etidronic Acid; Female; Humans; Male; Middle Aged; Osteoarthritis, Knee; Peptides; Radiography; Risedronic Acid

To determine whether risedronate (RIS) slows down trabecular bone loss in the medial compartment of the proximal tibia, a characteristic of patients with progressive knee osteoarthritis (OA).. Initially, 100 patients were randomly selected from each treatment group (each N approximately 300) comprising placebo and RIS 5 mg/day, 15 mg/day and 50 mg/week from a double blind, multi-centre, placebo-controlled, 2 yr investigation of OA knee patients in North America. Using fluoroscopic semi-flexed standard radiography, baseline and exit knee radiographs were digitized by laser scanner. Following computerized measurement of minimum medial compartment joint space width, each group was subdivided into joint space narrowing (JSN) non-progressor or JSN-progressor (JSN >or=0.6 mm measured at any point post-baseline). Computerized method of fractal signature analysis (FSA) quantified longitudinal changes separately in horizontal and vertical trabeculae in region of interest (three-fourth width of tibial compartment x 6 mm height) in the medial compartment. Following the initial study, all JSN-progressor knees within the entire patient cohort (N = 1232) were similarly analysed.. OA knees in JSN non-progressor group had a slight decrease in FSA for vertical and horizontal trabeculae and showed no drug effect. In JSN-progressor knees, bone loss was greater in both placebo and RIS 5 mg/day groups compared with those in RIS 15 mg/day group in which trabeculae were retained, and in the RIS 50 mg/week group in which the vertical trabecular number increased significantly (P < 0.05).. This preliminary study showed that patients with marked cartilage loss (JSN>or=0.6 mm) receiving RIS 15 mg/day retained vertical trabecular structure, and those receiving RIS 50 mg/week increased vertical trabecular number, thereby preserving the structural integrity of subchondral bone in knee OA.

Topics: Adult; Aged; Bone Density Conservation Agents; Disease Progression; Dose-Response Relationship, Drug; Double-Blind Method; Etidronic Acid; Female; Humans; Knee Joint; Longitudinal Studies; Male; Middle Aged; Osteoarthritis, Knee; Osteoporosis; Radiography; Risedronic Acid; Tibia

Bisphosphonates have slowed the progression of osteoarthritis (OA) in animal models and have decreased pain in states of high bone turnover. The Knee OA Structural Arthritis (KOSTAR) study, which is the largest study to date investigating a potential structure-modifying OA drug, tested the efficacy of risedronate in providing symptom relief and slowing disease progression in patients with knee OA.. The study group comprised 2,483 patients with medial compartment knee OA and 2-4 mm of joint space width (JSW), as determined using fluoroscopically positioned, semiflexed-view radiography. Patients were enrolled in 2 parallel 2-year studies in North America and the European Union. These studies evaluated the efficacy of risedronate at dosages of 5 mg/day, 15 mg/day, 35 mg/week (in Europe), and 50 mg/week (in North America) compared with placebo in reducing signs and symptoms, as measured by the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index and patient global assessment (PGA) scores, and in slowing radiographic progression.. A reduction of approximately 20% in signs and symptoms, as measured by WOMAC subscales and PGA scores, was observed in all groups, with no treatment effect of risedronate demonstrated. Risedronate did not significantly reduce radiographic progression as measured by decreased JSW or using a dichotomous definition of progression (joint space loss of >or=0.6 mm). Thirteen percent of patients receiving placebo demonstrated significant disease progression over 2 years. A dose-dependent reduction in the level of C-terminal crosslinking telopeptide of type II collagen, a cartilage degradation marker associated with progressive OA, was seen in patients who received risedronate. No increase in the number of adverse events was demonstrated for risedronate compared with placebo.. Although risedronate (compared with placebo) did not improve signs or symptoms of OA, nor did it alter progression of OA, a reduction in the level of a marker of cartilage degradation was observed. A sustained clinically relevant improvement in signs and symptoms was observed in all treatment and placebo groups.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Bone Density Conservation Agents; Cartilage; Disease Progression; Etidronic Acid; Female; Humans; Male; Middle Aged; Osteoarthritis, Knee; Pain; Placebos; Radiography; Risedronic Acid; Severity of Illness Index; Treatment Outcome

Osteoporosis is widely prevalent in India and osteoporotic fractures are a common cause of morbidity and mortality. A survey was conducted to obtain information regarding views of Indian orthopaedic surgeons about criteria used for diagnosing and treating osteoporosis, and treatment duration with bisphosphonates, the recommended drugs for osteoporosis. The survey was carried out at Indian Orthopaedic Association Conference (IOACON) in November 2006 using two types of forms--form 'A' contained information pertaining to clinical history and assessed the duration of patients' compliance with bisphosphonates, while form 'B' contained information on investigations as well for the same cases and assessed the duration of treatment effect with risedronate and alendronate. Of 1,054 orthopaedic surgeons who participated, 591 answered form 'A' and 463 answered form 'B'. Results showed that 78% of orthopaedic surgeons diagnose osteoporosis based on clinical history and majority of them were willing to prescribe bisphosphonates. However, they believed that two-thirds of all patients took drugs for 6 months or less. Of 409 surgeons who answered the question on risedronate, 55% believed its treatment effect was seen within 3 months, as compared to only 35% of 350 surgeons who answered for alendronate. The survey results highlight the need to better manage certain aspects of osteoporosis as regards diagnosis, drug choice and treatment duration in India.

Topics: Alendronate; Bone Density Conservation Agents; Diphosphonates; Disease Progression; Etidronic Acid; Fractures, Bone; Health Care Surveys; Humans; India; Orthopedics; Osteoporosis; Risedronic Acid

To evaluate in patients with knee osteoarthritis (OA) the size changes in bone oedema and cysts over 24 months, and to contrast these changes with cartilage volume loss using quantitative magnetic resonance imaging.. 107 patients with knee OA, selected from a large trial evaluating the effect of a bisphosphonate, were analysed by magnetic resonance imaging at baseline and 24 months. Assessments of subchondral bone oedema and cysts, and cartilage volume were done.. At baseline, 86 patients showed the presence of at least one type of bone lesion: 71 oedema, 61 cysts and 51 both. At 24 months, although not statistically significant, the oedema total size change increased by 2.09 (SD 15.03) mm, and the cyst by 1.09 (8.13) mm; mean size change for the oedema was +0.38 (2.18) mm and -0.10 (4.36) mm for the cyst. When analysed according to subregions, an increase was found for the cyst size in the trochlea (+0.67 (2.74) mm, p = 0.02) and in the lateral tibial plateau (+0.15 (0.83) mm, p = 0.09), and for the oedema size in the medial tibial plateau (+1.73 (8.11) mm, p = 0.05). At 24 months, significant correlations were seen between the loss of cartilage volume and oedema size change in the medial condyle (-0.40, p = 0.0001) and the medial tibial plateau (-0.23, p = 0.03), and the changes in cyst size in the medial condyle (-0.29, p = 0.01). A multivariate analysis showed that the oedema size change was strongly and independently associated with medial cartilage volume loss (-0.31, p = 0.0004).. These data demonstrate that bone lesions are prevalent in knee OA. The correlation of the oedema and cyst size increase in the medial compartment over time with a greater loss of cartilage volume in this area underlines the importance of subchondral bone lesions in OA pathophysiology.

Topics: Analysis of Variance; Bone and Bones; Bone Cysts; Cartilage, Articular; Diphosphonates; Disease Progression; Edema; Etidronic Acid; Female; Femur; Fibrocartilage; Follow-Up Studies; Humans; Linear Models; Magnetic Resonance Imaging; Male; Middle Aged; Osteoarthritis, Knee; Patella; Risedronic Acid

Topics: Administration, Oral; Alkaline Phosphatase; Diphosphonates; Disease Progression; Etidronic Acid; Humans; Imidazoles; Osteitis Deformans; Remission Induction; Risedronic Acid; Zoledronic Acid

Anti-resorptive agents--including estrogen (E), calcitonin (CT), and bisphosphonates--are established in the treatment of osteoporosis. Intermittent administration of parathyroid hormone (PTH) stimulates bone formation and is a possible therapeutic agent for the restoration of bone mass. The purpose was to determine the effects of the anti-resorptive agents alone and in combination with intermittent PTH on bone formation in the mandible and a long bone in the aged ovariectomized (Ovx) rat. Female rats were ovariectomized or sham-operated. One year later, groups of Ovx rats were treated with E, CT, or the bisphosphonate, Risedronate (NE). Additional groups of Ovx rats were treated with each of these agents in combination with human PTH for 10 weeks. Estrogen treatment suppressed most indices of bone formation in the humerus and mandible, while NE decreased some indices of formation at the endocortical and endosteal surfaces of the mandible and humerus. Increased double-labeled surface and mineral apposition rates were observed only on the mandibular endosteal surfaces following CT treatment. When the anti-resorptive agents were combined with intermittent PTH, most indices of bone formation at all skeletal sites were substantially greater than those of the untreated Ovx controls as well as the E-, CT-, and NE-treated groups, respectively. These results provide additional evidence that established and emerging therapies for osteoporosis affect osseous tissues in the oral cavity, and this may influence the progression of diseases and/or aging changes at this site.

Topics: Analysis of Variance; Animals; Bone Resorption; Calcitonin; Calcium Channel Blockers; Diphosphonates; Disease Models, Animal; Disease Progression; Drug Combinations; Estrogens; Etidronic Acid; Female; Follow-Up Studies; Humans; Humerus; Mandible; Mandibular Diseases; Minerals; Osteogenesis; Osteoporosis; Ovariectomy; Parathyroid Hormone; Periosteum; Rats; Rats, Sprague-Dawley; Risedronic Acid