Etidronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women.

BACKGROUND: Osteoporosis is an abnormal reduction in bone mass and bone deterioration, leading to increased fracture risk. Etidronate belongs to the bisphosphonate class of drugs which act to inhibit bone resorption by interfering with the activity of osteoclasts - bone cells that break down bone tissue. This is an update of a Cochrane review first published in 2008. For clinical relevance, we investigated etidronate's effects on postmenopausal women stratified by fracture risk (low versus high). OBJECTIVES: To assess the benefits and harms of intermittent/cyclic etidronate in the primary and secondary prevention of osteoporotic fractures in postmenopausal women at lower and higher risk of fracture, respectively. SEARCH METHODS: We searched the Cochrane Central Register of Control Trials (CENTRAL), MEDLINE, Embase, two clinical trial registers, the websites of drug approval agencies, and the bibliographies of relevant systematic reviews. We identified eligible trials published between 1966 and February 2023. SELECTION CRITERIA: We included randomized controlled trials that assessed the benefits and harms of etidronate in the prevention of fractures for postmenopausal women. Women in the experimental arms must have received at least one year of etidronate, with or without other anti-osteoporotic drugs and concurrent calcium/vitamin D. Eligible comparators were placebo (i.e. no treatment; or calcium, vitamin D, or both) or another anti-osteoporotic drug. Major outcomes were clinical vertebral, non-vertebral, hip, and wrist fractures, withdrawals due to adverse events, and serious adverse events. We classified a study as secondary prevention if its population fulfilled one or more of the following hierarchical criteria: a diagnosis of osteoporosis, a history of vertebral fractures, a low bone mineral density T-score (≤ -2.5), or aged 75 years or older. If none of these criteria were met, we considered the study to be primary prevention. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. The review has three main comparisons: (1) etidronate 400 mg/day versus placebo; (2) etidronate 200 mg/day versus placebo; (3) etidronate at any dosage versus another anti-osteoporotic agent. We stratified the analyses for each comparison into primary and secondary prevention studies. For major outcomes in the placebo-controlled studies of etidronate 400 mg/day, we followed our original review by defining a greater than 15% relative change as clinically important. For all outcomes of interest, we extracted outcome measurements at the longest time point in the study. MAIN RESULTS: Thirty studies met the review's eligibility criteria. Of these, 26 studies, with a total of 2770 women, reported data that we could extract and quantitatively synthesize. There were nine primary and 17 secondary prevention studies. We had concerns about at least one risk of bias domain in each study. None of the studies described appropriate methods for allocation concealment, although 27% described adequate methods of random sequence generation. We judged that only 8% of the studies avoided performance bias, and provided adequate descriptions of appropriate blinding methods. One-quarter of studies that reported efficacy outcomes were at high risk of attrition bias, whilst 23% of studies reporting safety outcomes were at high risk in this domain. The 30 included studies compared (1) etidronate 400 mg/day to placebo (13 studies: nine primary and four secondary prevention); (2) etidronate 200 mg/day to placebo (three studies, all secondary prevention); or (3) etidronate (both dosing regimens) to another anti-osteoporotic agent (14 studies: one primary and 13 secondary prevention). We discuss only the etidronate 400 mg/day versus placebo comparison here. For primary prevention, we collected moderate- to very low-certainty evidence from nine studies (one to four years in length) including 740 postmenopausal women at lower risk of fractures. Compared to placebo, etidronate 400 mg/day probably results in little to no difference in non-vertebral fractures (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.20 to 1.61); absolute risk reduction (ARR) 4.8% fewer, 95% CI 8.9% fewer to 6.1% more) and serious adverse events (RR 0.90, 95% CI 0.52 to 1.54; ARR 1.1% fewer, 95% CI 4.9% fewer to 5.3% more), based on moderate-certainty evidence. Etidronate 400 mg/day may result in little to no difference in clinical vertebral fractures (RR 3.03, 95% CI 0.32 to 28.44; ARR 0.02% more, 95% CI 0% fewer to 0% more) and withdrawals due to adverse events (RR 1.41, 95% CI 0.81 to 2.47; ARR 2.3% more, 95% CI 1.1% fewer to 8.4% more), based on low-certainty evidence. We do not know the effect of etidronate on hip fractures because the evidence is very uncertain (RR not estimable based on very low-certainty evidence). Wrist fractures were not reported in the included studies. For secondary prevention, four studies (two to four years in length) including 667 postmenopausal women at higher risk of fractures provided the evidence. Compared to placebo, etidronate 400 mg/day may make little or no difference to non-vertebral fractures (RR 1.07, 95% CI 0.72 to 1.58; ARR 0.9% more, 95% CI 3.8% fewer to 8.1% more), based on low-certainty evidence. The evidence is very uncertain about etidronate's effects on hip fractures (RR 0.93, 95% CI 0.17 to 5.19; ARR 0.0% fewer, 95% CI 1.2% fewer to 6.3% more), wrist fractures (RR 0.90, 95% CI 0.13 to 6.04; ARR 0.0% fewer, 95% CI 2.5% fewer to 15.9% more), withdrawals due to adverse events (RR 1.09, 95% CI 0.54 to 2.18; ARR 0.4% more, 95% CI 1.9% fewer to 4.9% more), and serious adverse events (RR not estimable), compared to placebo. Clinical vertebral fractures were not reported in the included studies. AUTHORS' CONCLUSIONS: This update echoes the key findings of our previous review that etidronate probably makes or may make little to no difference to vertebral and non-vertebral fractures for both primary and secondary prevention.

Strontium ranelate as an adjuvant for fracture healing: clinical, radiological, and ultrasound findings in a randomized controlled study on wrist fractures.

UNLABELLED: This randomized and controlled study evaluated the effect of therapy with strontium ranelate on callus formation in wrist fractures and its incidence in wrist recovery. Radiographic healing, progression of clinical recovery, and callus quality with ultrasound were evaluated. No statistically significant benefit of therapy was found. INTRODUCTION: Fracture prevention is the main goal of any therapy for osteoporosis. Various drugs used in osteoporosis treatment have the theoretical premises to promote fracture healing and osseointegration. In this study, the effect of strontium ranelate on callus formation in wrist fractures was evaluated and whether it could lead to clinically relevant modification of wrist recovery; having strontium ranelate osteoinductive properties, it could be used, if effective, as an adjunct in fracture healing for a faster and functionally better recovery and, at the same time, in starting proper therapy in osteoporotic patients with fragility fractures. METHODS: We considered only patients older than 60 years who had suffered wrist fracture and received nonoperative treatment with manual reduction of the fracture and cast for 35 days. Forty patients were included and randomly assigned to one of two groups: group A [patients treated with calcium (1200 mg/day) and vitamin D (800 IU/day)] and group B [patients treated with calcium (1200 mg/day) and vitamin D (800 IU/day) associated with strontium ranelate 2 g daily]. Radiographic healing was evaluated through the bone callus formation, cortical continuity, and density of the callus. A clinical evaluation using Castaing's criteria was carried out 2 and 3 months following the fracture together with an ultrasound study of callus density and vessels. RESULTS: A parametric analysis of the X-ray data, clinical evaluation, and ultrasonography results showed that there were no statistically significant differences in the two groups (p > 0.05 for all data). CONCLUSION: In analyzing the data obtained, we concluded that strontium ranelate administered in acute phase did not improve nor accelerate wrist fracture healing in our population.

Résultats de la technique de Sauvé Kapandji dans les séquelles post-traumatiques du poignet

Introduction: L'intervention de Sauvé-Kapandji consiste à réaliser une arthrodèse radio-ulnaire distale associée à une pseudarthrose intentionnelle de l'ulna. Le but de cette étude était d'évaluer les résultats obtenus avec cette technique dans le traitement des désordres post-traumatiques du poignet. Matériels et méthodes: Cette étude rétrospective réalisée entre janvier 2005 et décembre 2014 a concerné huit patients. La lésion était une séquelle d'une fracture de Galéazzi (n=5) , un cal vicieux d'une fracture de l'extrémité inférieure du radius(n=2), et une arthrose post-traumatique du poignet(n=1). Tous les poignets étaient douloureux, avec limitation de la mobilité et restriction de la force de serrage de la main. Résultats: Au recul moyen de 16 mois (extrême 8 et 36 mois) la douleur a été soulagée chez six patients. La pronation moyenne a été améliorée de 46° à 75°, la supination de 51° à 77°, la flexion de 44,5° à.48°, et l'extension de 24° à 54°. L'angle d'inclinaison radiale moyen a été amélioré de 18° à 20°, l'angle d'inclinaison de la glène moyen de 9,75°à 12°, et l'index radio-ulnaire distale de + 3 mm à +1mm. La force de serrage a été satisfaisante chez six patients cas et mauvaise chez deux. Toutes les arthrodèses ont fusionné. Conclusion: La technique de Sauvé Kapandji a permis le soulagement de la douleur, le renforcement de la mobilité et de la force de préhension chez la majorité des patients

Vitamin C to Prevent Complex Regional Pain Syndrome in Patients With Distal Radius Fractures: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: To determine whether vitamin C is effective in preventing complex regional pain syndrome (CRPS) in patients with distal radius fractures. DATA SOURCES: MEDLINE (1946 to present), EMBASE (1974 to present), and The Cochrane Library (no date limit) were systematically searched up to September 6, 2014, using MeSH and EMTREE headings with free text combinations. STUDY SELECTION: Randomized trials comparing vitamin C against placebo were included. No exclusions were made during the selection of eligible trials on the basis of patient age, sex, fracture severity, or fracture treatment. DATA EXTRACTION: Two reviewers independently screened articles, extracted data, and applied the Cochrane Risk of Bias tool. Evidence was graded using the Grading of Recommendations Assessment, Development, and Evaluation approach. DATA SYNTHESIS: Heterogeneity was quantified using the χ test and the I statistic. Outcome data were combined with a random effects model. RESULTS: Across 3 trials (n = 890) of patients with distal radius fractures, vitamin C did not reduce the risk for CRPS (risk ratio = 0.45; 95% confidence interval, 0.18-1.13; I = 70%). This result was confirmed in sensitivity analyses to test the importance of missing data because of losses to follow-up under varying assumptions. Heterogeneity was explained by diagnostic criteria, but not regimen of vitamin C or fracture treatment. CONCLUSIONS: The evidence for vitamin C to prevent CRPS in patients with distal radius fractures fails to demonstrate a significant benefit. The overall quality of the evidence is low, and these results should be interpreted in the context of clinical expertise and patient preferences.

The influence of vitamin C on the outcome of distal radial fractures: a double-blind, randomized controlled trial.

BACKGROUND: Vitamin C has been proposed to improve outcomes after a distal radial fracture by promotion of bone and soft-tissue healing and reduction of the prevalence of complex regional pain syndrome (CRPS). Our primary aim was to examine the effect of vitamin C on functional outcome after a distal radial fracture. METHODS: A total of 336 adult patients with an acute fracture of the distal aspect of the radius were recruited over a one-year period and randomized to receive 500 mg of vitamin C or placebo daily for fifty days after the fracture. The primary outcomes were the DASH (Disabilities of the Arm, Shoulder and Hand) score at six weeks and at one year. Secondary variables included complications, wrist and finger motion, grip and pinch strength, pain, and a CRPS score. RESULTS: There were no significant differences in patient or fracture characteristics between the treatment groups. There was no significant effect of vitamin C on the DASH score throughout the study period. At six weeks, patients in the vitamin C group with a nondisplaced fracture had a significantly greater wrist flexion deficit (p = 0.008) and pinch strength deficit (p = 0.020) and a greater rate of CRPS (p = 0.022), but there was no difference in the CRPS rate at any other time point. At twenty-six weeks, there was a higher rate of complications (p = 0.043) and greater pain with use (p = 0.045) in the patients with a displaced fracture treated with vitamin C. There was no significant difference in the time to fracture-healing. CONCLUSIONS: This study demonstrated no significant difference at one year in the DASH score, other functional outcomes, the rate of CRPS, or osseous healing of nondisplaced or displaced distal radial fractures treated with vitamin C compared with placebo. We conclude that administration of vitamin C confers no benefit to patients with a displaced or nondisplaced fracture of the distal aspect of the radius. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Use of bone morphogenetic protein-2 (rh-BMP-2) in treatment of wrist and hand nonunion with comparison to historical control groups.

The purpose of this study is to report the percentage of patients achieving union, time to union, and complications with the use of bone morphogenetic protein-2 (rh-BMP-2) in surgical repair of established nonunion in the hand and wrist. Twenty-seven patients with nonunion of the hand and wrist were treated between 2005 and 2011 with surgical repair and augmentation using 4.2 mg of rh-BMP-2. Sites of nonunion included the phalanx (seven), carpus (nine), distal radius (five), and distal ulna (six). Radiographic union and complications were the primary and secondary outcomes, respectively. Eighty-nine percent (24/27) of patients achieved union within an average of 4.3 ± 2.8 months of surgery. There were no direct complications from administration of rh-BMP-2. Radiographic union was consistent with published rates for nonunion repair of scaphoid, phalanx, and distal radius fractures. Rh-BMP-2 did not produce superior rates of union in the patients with wrist and hand nonunion.

Finite element analysis based on in vivo HR-pQCT images of the distal radius is associated with wrist fracture in postmenopausal women.

UNLABELLED: BMD, bone microarchitecture, and bone mechanical properties assessed in vivo by finite element analysis were associated with wrist fracture in postmenopausal women. INTRODUCTION: Many fractures occur in individuals with normal BMD. Assessment of bone mechanical properties by finite element analysis (FEA) may improve identification of those at high risk for fracture. MATERIALS AND METHODS: We used HR-pQCT to assess volumetric bone density, microarchitecture, and microFE-derived bone mechanical properties at the radius in 33 postmenopausal women with a prior history of fragility wrist fracture and 33 age-matched controls from the OFELY cohort. Radius areal BMD (aBMD) was also measured by DXA. Associations between density, microarchitecture, mechanical parameters and fracture status were evaluated by univariate logistic regression analysis and expressed as ORs (with 95% CIs) per SD change. We also conducted a principal components (PCs) analysis (PCA) to reduce the number of parameters and study their association (OR) with wrist fracture. RESULTS: Areal and volumetric densities, cortical thickness, trabecular number, and mechanical parameters such as estimated failure load, stiffness, and the proportion of load carried by the trabecular bone at the distal and proximal sites were associated with wrist fracture (p < 0.05). The PCA revealed five independent components that jointly explained 86.2% of the total variability of bone characteristics. The first PC included FE-estimated failure load, areal and volumetric BMD, and cortical thickness, explaining 51% of the variance with an OR for wrist fracture = 2.49 (95% CI, 1.32-4.72). Remaining PCs did not include any density parameters. The second PC included trabecular architecture, explaining 12% of the variance, with an OR = 1.82 (95% CI, 0.94-3.52). The third PC included the proportion of the load carried by cortical versus trabecular bone, assessed by FEA, explaining 9% of the variance, and had an OR = 1.61 (95% CI, 0.94-2.77). Thus, the proportion of load carried by cortical versus trabecular bone seems to be associated with wrist fracture independently of BMD and microarchitecture (included in the first and second PC, respectively). CONCLUSIONS: These results suggest that bone mechanical properties assessed by microFE may provide information about skeletal fragility and fracture risk not assessed by BMD or architecture measurements alone and are therefore likely to enhance the prediction of wrist fracture risk.

Low frequency of treatment of osteoporosis among postmenopausal women following a fracture.

BACKGROUND: Osteoporosis is a major cause of morbidity. Treatment of osteoporosis reduces the risk of fracture, particularly for postmenopausal women with a history of fracture. METHODS: A retrospective study was conducted using the automated databases of 7 health maintenance organizations to evaluate the use of drugs recommended for secondary prevention of osteoporotic fracture. Women 60 years and older with an inpatient or outpatient diagnostic code for a fracture of the hip, vertebra, or wrist between October 1, 1994, and September 30, 1996, and at least 1 year of continuous enrollment with a drug benefit plan following the date of fracture, were identified. The frequency of use of medications for the treatment of osteoporosis (estrogen replacement therapy, bisphosphonates, and calcitonin) during the 1-year period following the date of the initial fracture was estimated overall and according to patient age, fracture site, and year of fracture. RESULTS: During the study period, 3492 women 60 years and older were diagnosed with a fracture of the hip, vertebra, or wrist, and met the inclusion criteria. Of these patients, 822 (24%) received a drug for osteoporosis treatment during the year following the fracture. The proportion of women receiving treatment for osteoporosis was approximately 2-fold higher among those with a fracture of the vertebra (44%) than among those with a fracture of the hip (21%) or wrist (23%) (P<.001). Of the 2605 women who had not been treated for osteoporosis in the 90 days before a fracture, 14% received treatment for osteoporosis in the year following a fracture. Increasing age was associated with a reduced likelihood of receiving osteoporosis treatment (P<.001). CONCLUSIONS: Most of the older women who had experienced a fracture of the hip, vertebra, or wrist did not receive drug treatment for osteoporosis within 1 year following the fracture. Interventions to improve the detection and treatment of osteoporosis in high-risk patients need to be developed.

Diagnosis and treatment of injury to the second and third carpometacarpal joints.

We describe the diagnosis, treatment, and follow-up of a group of 13 patients with hand pain traced to pathologic conditions of the second or third carpometacarpal joints. Missed diagnosis was universal. With suspicion raised by history of injury or repeated stress and point tenderness on examination, diagnosis was confirmed by complete pain relief after injection of 1% lidocaine locally. In management of patients with occult pain in the hand, attention should be directed to the second or third carpometacarpal joints. Arthrodesis with use of an inverted triangular graft from the base of the metacarpal provides predictable and lasting relief.

[Diflunisal, a new analgesic, and oxyphenbutazone in the treatment of sprains and dislocations (author's transl)]. / Diflunisal, ein neues Analgetikum, und Oxyphenbutazon bei der Behandlung von Zerrungen und Verrenkungen.

In a randomized double-blind study efficacy and tolerance of diflunisal, 375 mg twice daily, and oxyphenbutazone, 200 mg twice daily, were compared in 40 patients (aged 21 to 70 years, average 38 years), with moderate or severe complaints after spraining or dislocating ankle or wrist. The drugs were given for five days. Both proved to be highly efficacious, diflunisal slightly more so. Among the 20 patients in the diflunisal group one developed diarrhoea, another gastritis; in the oxyphenbutazone group one developed gastritis, another herpetiform pustules. There were no clinically significant abnormalities in routine biochemical tests.