Are bisphosphonates efficacious in knee osteoarthritis? A meta-analysis of randomized controlled trials.

OBJECTIVE: To clarify the effects of bisphosphonates in knee osteoarthritis (OA) using an up-to-date meta-analysis of randomized controlled trials (RCTs). DESIGN: The protocol is registered in PROSPERO (CRD42017073449). We searched MEDLINE, EMBASE, Google Scholar, Web of Science, and Cochrane Database from inception until August 2017. We included only RCTs comparing any bisphosphonates vs placebo in knee OA patients and reporting validated pain and function scales, radiographic progression, and adverse events (AEs) outcomes. We excluded studies using active comparators or concomitant medications besides non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen. We calculated standardized mean differences (SMDs) to account for variation in outcome scales. Random effects meta-analyses were performed. RESULTS: We included seven RCTs (3013 patients, 69% female); most patients (N = 2767) received oral risedronate. No pain or function outcomes, regardless of dose, route, time point or measuring instrument, revealed statistically significant results (end of trial pain SMD = -0.16 [95% confidence interval (CI): -0.34, 0.02]). Similarly, we found no statistically significant effect on radiographic progression (risk ratio = 0.98 [95% CI: 0.77, 1.26]). One small RCT in patients with bone marrow lesions (BMLs) suggested a reduction in BML size at 6 months. Bisphosphonates displayed good tolerability, with no statistically significant differences in AE outcomes vs placebo. CONCLUSIONS: Contrary to prior reviews, our analysis showed that bisphosphonates neither provide symptomatic relief nor defer radiographic progression in knee OA. However, these agents may still be beneficial in certain subsets of patients who display high rates of subchondral bone turnover. Future studies should be directed at defining such OA subsets and investigating the effects of bisphosphonates in those patients.

Behavioral and psychological disorders in uninfected children aged 6 to 11 years born to human immunodeficiency virus-seropositive mothers.

This study investigated the behavioral and psychological differences between 39 uninfected children born to human immunodeficiency virus (HIV)-seropositive mothers (HIV-seroreverter [SR]) and 78 children with no family history of HIV infection. Caretakers completed the Child Behavior Checklist and the Gittelman modification of the Conners' Parent's Questionnaire, whereas children completed the Children's Manifest Anxiety Scale and the Children's Depression Inventory. In 14 SR children and 28 controls, narrative task was also evaluated. The personalities of SR children, as measured by the caretaker-completed scales, revealed significantly more problems of social adjustment and attention and more externalizing symptoms than did the personalities of control children. On the child-completed scales, SR children showed significantly more anxiety and depression than did controls. Caretakers reported consistently fewer symptoms of anxiety and depression in the children than did the children themselves. Difficulties in verbal recall included aspects of depressive and anxious feelings; on the narrative task measure, SR children showed poorer skill in free verbal recall than did control children, and they simplified episodes with mixed emotions. In addition, ambiguous episodes elicited significantly more negative feelings in SR children than in controls. These findings show that there is a great necessity for assisting SR children. It will be important to determine whether these children will remain at risk for emotional consequences in their adult lives.

Beta-endorphin levels in peripheral blood mononuclear cells and long-term naltrexone treatment in autistic children.

We assessed the clinical and biological effects of high-dose, long-term Naltrexone (NTX) treatment in 11 children (3-11 years), who had been diagnosed as autistic. The drug was given following an open design, for 12 weeks. Beta-Endorphin (beta-END) was assayed in peripheral blood mononuclear cells after 1 and 3 months of treatment, and 6 months after the completion of the course. Baseline beta-END levels were higher than in healthy age-matched controls. In seven patients treatment reduced beta-END, whose levels rose in four children. Autistic symptoms were considerably attenuated in all cases, with functional improvements involving several areas. There was a close correlation between the reduction in beta-END levels and the decrease of social withdrawal, and an evident--though weak--correlation between increases in beta-END and decreases in stereotypy and abnormal speech. Both effects persisted after treatment stopped.