Persistence and adherence to parenteral osteoporosis therapies: a systematic review.

Osteoporosis is a chronic disease of low bone mass and fragility. Treatment is frequently compromised by suboptimal medication compliance causing increased morbidity. This review investigates adherence and persistence to parenteral osteoporosis therapies. Findings reveal parenteral medications requiring reduced dosing frequency have higher compliance than oral therapies. This systematic review examines real-world adherence to parenteral osteoporosis therapies. We searched PubMed, Medline, and EMBASE databases for English language observational studies that examined patient adherence and/or persistence to parenteral osteoporosis treatments (teriparatide sc, ibandronate iv, zoledronic acid iv, and denosumab sc) in adults with osteoporosis published up to September 2018. Studies with only self-reported adherence or persistence data and those with less than 20 patients were excluded. Quality assessment of included studies was completed using the Newcastle-Ottawa quality assessment scale (NOS). We identified 40 eligible studies. Teriparatide was examined in 29 studies, with persistence rates of 10-87% (median 55%) at 1 year and 10-69% (median 29.5%) at 2 years, and adherence rates of 21-89% (median 53%) at 1 year and 37-68% (median 40%) at 2 years. Ten studies of zoledronic acid reported persistence rates of 34-73% (median 42%) for second dose and 20-54% (median 35.8%) for third dose. Ten studies of ibandronate adherence reported and 2-year persistence rates of 31-58% (median 47.5%) in 1 year and 13-35% (median 25%) at 2 years, and adherence rates of 21-72% (median 47.3%) and 15-58% (median 36.5%) respectively. Denosumab was reported in 19 studies, with second (1 year) and fourth (2 year) dose persistence rates of 61-100% (median 81%) and 36-99% (median 45.5%). There is substantial heterogeneity in reports of persistence and adherence rates with parenteral osteoporosis therapies. Most of the published data are from short-term studies and evaluations of long-term adherence and persistence with parenteral therapies for osteoporosis are needed.

Calcitonin for treating acute and chronic pain of recent and remote osteoporotic vertebral compression fractures: a systematic review and meta-analysis.

Vertebral collapse is a common fracture associated with osteoporosis. Subsequent pain may be severe and often requires medications and bed rest. Several studies have suggested the use of calcitonin for the treatment of fracture pain. We sought to determine the analgesic efficacy of calcitonin for acute and chronic pain of osteoporotic vertebral compression fractures (OVCF). We searched for randomized, placebo, and controlled trials that evaluated the analgesic efficacy of calcitonin for pain attributable to OVCFs. We performed meta-analyses to calculate standardized mean differences (SMDs) using a fixed or random effects model. The combined results from 13 trials (n = 589) determined that calcitonin significantly reduced the severity of acute pain in recent OVCFs. Pain at rest was reduced by week 1 [mean difference (MD) = -3.39, 95% confidence interval (CI) = -4.02 to -2.76), with continued improvement through 4 weeks. At week 4, the difference in pain scores with mobility was even greater (SMD = -5.99, 95% CI = -6.78 to -5.19). For patients with chronic pain, there was no statistical difference between groups while at rest; there was a small, statistically significant difference between groups while mobile at 6 months (SMD = 0.49, 95% CI = -0.85 to -0.13, p = 0.008). Side effects were mild, with enteric disturbances and flushing reported most frequently. Although calcitonin has proven efficacy in the management of acute back pain associated with a recent OVCF, there is no convincing evidence to support the use of calcitonin for chronic pain associated with older fractures of the same origin.

Lung transplantation for severe antineutrophilic cytoplasmic antibody-associated vasculitis.

Antineutrophil cytoplasmic antibody-associated vasculitis is a life-threatening disorder for which medical therapy has greatly improved survival. However, there is still significant mortality associated with antineutrophil cytoplasmic antibody-associated vasculitis. Little data exists on the utility of lung transplantation for patients, especially with an acute and severe form of this disease. Herein, we report successful lung transplantation for a patient with life-threatening pulmonary hemorrhage and respiratory failure as a consequence of this pulmonary renal syndrome.

Clinical guidelines: a must for rheumatology?

Clinical guidelines are sets of recommendations, backed by medical evidence, to aid physicians in patient-care decisions. There has been a proliferation of practice guideline development in all fields of medicine, including rheumatology. This chapter will discuss the need for guidelines in rheumatology, the methodology of guideline development, validation and implementation, the various guidelines published in rheumatology, and the role of the rheumatologist in guideline development. Clinical guidelines can serve to inform practitioners of the latest medical evidence and minimize harmful practice variation. Guidelines must rely on good evidence to be credible to the medical community, yet there are still many barriers to guideline acceptance by practitioners. The theories behind guideline development and validation are well described, although not always practised. Guideline dissemination and implementation methods are still being explored. It remains unclear how best to implement guidelines and convince physicians to accept and incorporate evidence-based recommendations into their practice.

Identifying clinical trials in the medical literature with electronic databases: MEDLINE alone is not enough.

The objective of this study was to compare the performance of MEDLINE and EMBASE for the identification of articles regarding controlled clinical trials (CCTs) published in English and related to selected topics: rheumatoid arthritis (RA), osteoporosis (OP), and low back pain (LBP). MEDLINE and EMBASE were searched for literature published in 1988 and 1994. The initial selection of papers was then reviewed to confirm that the articles were about CCTs and to assess the quality of the studies. Selected journals were also hand searched to identify CCTs not retrieved by either database. Overall, 4111 different references were retrieved (2253 for RA, 978 for OP, and 880 for LBP); 3418 (83%) of the papers were in English. EMBASE retrieved 78% more references than MEDLINE (2895 versus 1625). Overall, 1217 (30%) of the papers were retrieved by both databases. Two hundred forty-three papers were about CCTs. Two-thirds of these were retrieved by both databases, and one-third by only one. An additional 16 CCTs not retrieved by either database were identified through hand searching. Taking these into account, EMBASE retrieved 16% more CCTs than MEDLINE (220 versus 188); the EMBASE search identified 85% of the CCTs compared to 73% by MEDLINE. No significant differences were observed in the mean quality scores and sample size of the CCTs missed by MEDLINE compared to those missed by EMBASE. Our findings suggest that the use of MEDLINE alone to identify CCTs is inadequate. The use of two or more databases and hand searching of selected journals are needed to perform a comprehensive search.

Antimalarials for treating rheumatoid arthritis.

OBJECTIVES: To assess the short-term efficacy and toxicity of antimalarials for the treatment of rheumatoid arthritis (RA). SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group's trials register, the Cochrane Controlled Trials Register, Medline and Embase up to and including August 2000. We also carried out a handsearch of the reference lists of the trials retrieved from the electronic search. SELECTION CRITERIA: All randomized controlled trials (RCTs) and controlled clinical trials (CCTs) comparing antimalarials against placebo in patients with RA DATA COLLECTION AND ANALYSIS: Data abstraction was carried out independently by two reviewers. The same two reviewers using a validated checklist (Jadad 1996) assessed the methodological quality of the RCTs and CCTs. Rheumatoid arthritis outcome measures were extracted from the publications for the 6-month endpoint. The pooled analysis was performed using standardized mean differences for joint counts, pain and global assessments. Weighted mean differences were used for erythrocyte sedimentation rate (ESR). Toxicity was evaluated with pooled odds ratios for withdrawals. A chi-square test was used to assess heterogeneity among trials. Fixed effects models were used throughout. MAIN RESULTS: We found four trials, with 300 patients randomized to hydrochloroquine and 292 to placebo. Only trials evaluating hydroxychloroquine could be pooled in the analysis. A statistically significant benefit was observed when hydroxychloroquine was compared to placebo. The standardized mean differences for the various outcome measures ranged from -0.33 to -0.52, and were statistically significant. Statistically significant differences were also observed for ESR. Overall withdrawals and withdrawals due to lack of efficacy were significantly more frequent in the placebo group. No differences were observed in withdrawals due to toxicity. REVIEWER'S CONCLUSIONS: Hydroxychloroquine appears to be efficacious for the treatment of RA. Its overall effect appears to be moderate, but its low toxicity profile should be considered when treating patients with RA.

Calcium and vitamin D for corticosteroid-induced osteoporosis.

OBJECTIVES: To assess the effects of calcium and vitamin D compared to calcium alone or placebo in the prevention of bone loss in patients taking systemic corticosteroids. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal trials register, Cochrane Controlled Trials Register, EMBASE and Medline up to 1996. We also conducted a hand search of abstracts from various scientific meetings and reference lists of selected trials. SELECTION CRITERIA: All randomized trials comparing calcium and vitamin D to calcium alone or placebo in patients taking systemic corticosteroids. DATA COLLECTION AND ANALYSIS: Data was abstracted from trials by two investigators. Methodological quality was assessed in a similar manner. Analysis was performed using fixed effects models. MAIN RESULTS: Five trials were included, with 274 patients. The analysis was performed at two years after starting calcium and vitamin D. There was a significant weighted mean difference (WMD) between treatment and control groups in lumbar (WMD 2.6 (95% CI 0.7, 4.5), and radial bone mineral density (WMD 2.5 (95% CI 0.6, 4.4). The other outcome measures (femoral neck bone mass, fracture incidence, biochemical markers of bone resorption) were not significantly different. REVIEWER'S CONCLUSIONS: This meta-analysis demonstrated a clinically and statistically significant prevention of bone loss at the lumbar spine and forearm with vitamin D and calcium in corticosteroid treated patients. Because of low toxicity and cost all patients being started on corticosteroids should receive prophylactic therapy with calcium and vitamin D.

Antimalarials for rheumatoid arthritis.

OBJECTIVES: To estimate the short-term efficacy and toxicity of antimalarials for the treatment of rheumatoid arthritis (RA). SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group's trials register, the Cochrane Controlled Trials Register, Medline and Embase up to and including July 1997. We also carried out a handsearch of the reference lists of the trials retrieved from the electronic search. SELECTION CRITERIA: All randomized controlled trials (RCTs) and controlled clinical trials (CCTs) comparing antimalarials against placebo in patients with RA DATA COLLECTION AND ANALYSIS: Data abstraction was carried out independently by two reviewers. The same two reviewers using Jadad's scale (Jadad 1995) assessed the methodological quality of the RCTs and CCTs. Rheumatoid arthritis outcome measures were extracted from the publications for the 6-month endpoint. The pooled analysis was performed using standardized mean differences for joint counts, pain and global assessments. Weighted mean differences were used for erythrocyte sedimentation rate (ESR). Toxicity was evaluated with pooled odds ratios for withdrawals. A chi-square test was used to assess heterogeneity among trials. Fixed effects models were used throughout. MAIN RESULTS: We found four trials, with 300 patients randomized to hydrochloroquine and 292 to placebo. Only trials evaluating hydroxychloroquine could be pooled in the analysis. A statistically significant benefit was observed when hydroxychloroquine was compared to placebo. The standardized mean differences for the various outcome measures ranged from -0.33 to -0. 52, and were statistically significant. Statistically significant differences were also observed for ESR. Overall withdrawals and withdrawals due to lack of efficacy were significantly more frequent in the placebo group. No differences were observed in withdrawals due to toxicity. REVIEWER'S CONCLUSIONS: Hydroxychloroquine appears to be efficacious for the treatment of RA. Its overall effect appears to be moderate, but its low toxicity profile should be considered when treating patients with RA.

Bisphosphonates for steroid induced osteoporosis.

OBJECTIVES: To assess the effects of bisphosphonates for the prevention and treatment of corticosteroid-induced osteoporosis. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group trials register, Medline up to 1997 and Embase1988-1997), and selected hand searching of reference lists was conducted. Hand searching of scientific abstracts from relevant meetings for the last five years was also done. An electronic search in Current Contents was done for the last six months. The Cochrane Controlled Trials Register (CCTR) will be searched for future updates. All languages were included in the search. For practical reasons only those in English were included, but all languages will be retrieved and translated for future updates. SELECTION CRITERIA: All controlled clinical trials (CCTs) dealing with prevention or treatment of corticosteroid-induced osteoporosis with bisphosphonates of any type and reporting the outcomes of interest were assessed. Trials had to involve adults only, and subjects had to be taking a mean steroid dose of 7.5 mg/day or more. DATA COLLECTION AND ANALYSIS: All data extraction was performed by two independent reviewers. Outcomes of interest included change in bone mineral density (BMD) at the lumbar spine and femoral neck at six and 12 months. If present, data on number of new fractures and withdrawals due to adverse effects were also extracted. All data extraction was performed by two independent reviewers. Both continuous and dichotomous data were analyzed using fixed effects models. When significant heterogeneity was present, a random effects model was used. MAIN RESULTS: A total of 13 trials, including 842 patients are included in this meta-analysis. Results are reported as a weighted mean difference of the percent change in BMD between the treatment and placebo groups, with trials being weighted by the inverse of their variance. The 95% confidence intervals (95% CI) are presented. At the lumbar spine, the weighted mean difference of BMD between the treatment and placebo groups was 4.3% (95% CI 2.7, 5.9). At the femoral neck, the weighted mean difference was 2.1% (95%CI 0. 01, 3.8). Although there was a 24% reduction in odds of spinal fractures [OR 0.76 (95%CI 0.37, 1.53)], this result was not statistically significant. REVIEWER'S CONCLUSIONS: Bisphosphonates are effective at preventing and treating corticosteroid-induced bone loss at the lumbar spine and femoral neck. Efficacy regarding fracture prevention cannot be concluded from this analysis, although bone density changes are correlated with fracture risk.

Calcitonin for the treatment and prevention of corticosteroid-induced osteoporosis.

BACKGROUND: Corticosteroid-induced osteoporosis is a cause of morbidity in patients with chronic obstructive lung disease, asthma, and rheumatologic disorders. Corticosteroid treatment causes bone loss by a variety of complex mechanisms. It has been shown that bone mineral loss at the hip averages 14% in the first year after starting corticosteroid therapy. OBJECTIVES: To review the efficacy of calcitonin (subcutaneous or nasal) for the treatment and prevention of corticosteroid-induced osteoporosis. SEARCH STRATEGY: We conducted a search of Medline, the Cochrane Controlled Trials Register and Embase using the Cochrane Musculoskeletal Group search strategy for randomized controlled trials (RCTs) up to May 1998. We also searched bibliographic references and consulted content experts. SELECTION CRITERIA: Two independent reviewers selected RCTs which met predetermined inclusion criteria. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data using predetermined forms and assessed methodological quality of randomization, blinding and dropouts. For dichotomous outcomes, relative risks (RR) were calculated. For continuous data, weighted mean differences (WMD) of the percent change from baseline were calculated. We decided a priori to use random effects models for all outcomes, because of uncertainty about whether a consistent true effect exists in such different populations. MAIN RESULTS: Nine trials met the inclusion criteria, including 221 patients randomized to calcitonin and 220 to placebo. The median methodologic quality was two out of a maximum of five points. Calcitonin was more effective than placebo at preserving bone mass at the lumbar spine after six and 12 months of therapy with a WMD of 2.8% (95% CI: 1.4 to 4.3) and 3.2% (95% CI: 0.3 to 6.1). At 24 months, lumbar spine BMD was not statistically different between groups: WMD 4.5% (95% CI: -0.6 to 9.5)]. Bone density at the distal radius was also higher with calcitonin after six months of therapy, but bone density at the femoral neck was not different between placebo and calcitonin treated groups. The relative risk of fractures was not significantly different between calcitonin and placebo with a relative risk (RR) of 0.71 (95% CI: 0.26 to 1.89) for vertebral and 0.52 (95% CI: 0.14 to 1.96) for nonvertebral fractures. The subgroup analyses of methodological quality and duration of corticosteroid therapy were confounded. Trials of patients who had been taking steroids for greater than three months (which were of low methodologic quality) demonstrated a larger effect of calcitonin on spine bone density (about 6%) than prevention trials (about 1%). There was no consistent effect of different dosages (50-100 IU compared to 200-400 IU). However, subcutaneous calcitonin showed substantially greater prevention of bone loss. Withdrawals due to side effects were higher in the calcitonin-treated groups: RR 3.19 (95%CI: 0.66 to 15.47). Important side effects included nausea and facial flushing. REVIEWER'S CONCLUSIONS: Calcitonin appears to preserve bone mass in the first year of glucocorticoid therapy at the lumbar spine by about 3% compared to placebo, but not at the femoral neck. Our analysis suggests that the protective effect on bone mass may be greater for the treatment of patients who have been taking corticosteroids for more than three months. Efficacy of calcitonin for fracture prevention in steroid-induced osteoporosis remains to be established.

A metaanalysis on the use of bisphosphonates in corticosteroid induced osteoporosis.

OBJECTIVE: To conduct a metaanalysis on the use of bisphosphonates in corticosteroid induced osteoporosis. METHODS: A Cochrane systematic review including electronic database searching (MEDLINE and EMBASE), and selected hand searching of reference lists and scientific abstracts was conducted. Metaanalysis using random and fixed effects modeling was used on the selected trials to calculate summary effect measures. All controlled clinical trials dealing with prevention or treatment of corticosteroid induced osteoporosis with bisphosphonates of any type and reporting the outcome of interest were assessed. Trials had to involve adults only, and subjects had to be taking a mean steroid dose of 7.5 mg/day or more. Outcomes of interest were change in bone mineral density (BMD) at the lumbar spine and femoral neck at 6 and 12 months. If present, data on number of new fractures and adverse effects were also extracted. The extraction was performed by 2 independent reviewers. RESULTS: Results are reported as a weighted mean difference in the percentage change in BMD between the treatment and placebo groups, with trials being weighted by the inverse of their variance. At the lumbar spine the weighted mean difference between the treatment and placebo groups was 4.0% (95% CI 2.5, 5.5). At the femoral neck the weighted mean difference was 2.1% (95% CI 0.2, 4.0). Although there was a 24% reduction in spinal fractures, this result did not reach statistical significance. CONCLUSION: Bisphosphonates are effective at preventing and treating corticosteroid induced bone loss at the lumbar spine. Efficacy regarding fracture prevention cannot be concluded from this analysis, although bone density changes are correlated with fracture risk. Bisphosphonates are less efficacious at preventing or treating corticosteroid induced osteoporosis at the femoral neck.

Attitudes and beliefs of family physicians and gynecologists in relation to the prevention and treatment of osteoporosis.

The objective of this study was to evaluate the attitudes and beliefs of primary care physicians (PCPs) and obstetricians/gynecologists (O&Gs) in relation to the prevention and treatment of osteoporosis (OP) in postmenopausal women. A survey was mailed to a random sample of PCPs and to all O&Gs registered in the province of Alberta (Canada). The survey evaluated their practice patterns using closed-ended questions, Likert scaled items, and two case studies. Cases 1 and 2 were 52-year-old and 62-year-old healthy postmenopausal women, respectively, with no known risks for OP. Neither had received hormone replacement therapy (HRT). One hundred fifty-seven PCPs and 57 O&Gs participated in the study. Thirty-eight percent of the PCPs and 32% of the O&Gs stated that they never requested bone mineral density measurements (BMDm) in early postmenopausal women. Most would request BMDm only in the presence of risk factors. The most important criteria to request BMDm were chronic glucocorticoid use and recent fractures. For case 1, 7% of the PCPs and 11% of the O&Gs would request BMDm; 76% of the PCPs and 80% of the O&Gs would recommend HRT. For case 2, 29% of the PCPs and 47% of the O&Gs would request BMDm (p = 0.01); 43% of the PCPs and 49% of the O&Gs would prescribe HRT. In general, O&Gs were more inclined to intervene in relation to BMDm and HRT. O&Gs were also more likely to be influenced by clinical trials than PCPs (p < 0.001). Our findings show variations in the patterns of practice of physicians in relation to the prevention of OP. In general, use of densitometry appears to be low. The results of the case studies suggest that individual physician perceptions may be more influential than patient characteristics when requesting BMDm and prescribing HRT, particularly in older postmenopausal women. This group of healthy older women have approximately equal odds of being offered versus not being offered BMDm and HRT according to the physician they consult.

[The effect of location and shape of the fracture line on results of conservative treatment of closed tibial shaft fractures]. / Wplyw umiejscowienia i przebiegu szczeliny zlamania na wyniki zachowawczego leczenia zamknietych zlaman trzonów kosci goleni.

One hundred seventy five closed crural shafts fractures have been analysed. They have been classified depending on the location and shape of the fracture line. Clinical and radiological assessment were taken into consideration. The best final results have been achieved in fractures of middle third of the tibia and in fractures of transverse fracture line. The disturbances of bone union most often occurred between middle and distal third of the tibia and transverse fractures.

[Use of supra-malleolar traction in treatment of closed fractures of the crural shafts]. / Zastosowanie wyciagu nadkostkowego w leczeniu zamknietych zlaman trzonów kosci goleni.

The results of treatment of 36 closed fractures of the crural shafts reduced with supra-malleolar traction have been presented and evaluated with own scale. The best results were achieved with traction maintained for 5-6 weeks. Most of the failures were due to the disturbed union and restricted range of movement in the ankle. The authors conclude, that traction prevents secondary displacement and should be recommended for treatment of unstable fractures of the crural shafts.

Reversible interleukin-2 response defects in systemic lupus erythematosus.

Limiting dilution analysis techniques were used to determine precursor frequencies for interleukin-2 (IL-2) responsive cells among the peripheral blood lymphocytes of patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis compared with healthy subjects. Response defects in SLE were found, but were of two types: reduced precursor frequencies with normal pattern of response (single-hit kinetics); and abnormal multi-hit responsiveness. These abnormalities were not more frequent statistically in those with active disease. Precursor frequencies of SLE peripheral blood lymphocytes were enhanced by resting the cells for up to 72 h prior to activation, and by adding exogenous IL-2 during the initial activation step. The IL-2 response defects of SLE are therefore reversible and may in part be secondary to other in vivo abnormalities, such as deficient IL-2 production.