Are bisphosphonates effective in treating osteoporosis in children and adults with cystic fibrosis?—A Cochrane review summary with commentary

2.1 What is the aim of this Cochrane review?

The aim of this Cochrane Review was to evaluate the impact of bisphosphonates on fracture rates, BMD, quality of life, adverse events, trial discontinuations, and survival in individuals diagnosed with CF.

2.2 What was studied in the Cochrane review?

The population addressed in this review was individuals of any age or gender diagnosed with CF, either clinically or through sweat and genetic testing, encompassing all levels of disease severity and BMD. The interventions studied were randomized controlled trials that compared bisphosphonates to control groups (other bisphosphonates, placebos, or standard treatments) for the management or prevention of osteoporosis in individuals with CF. All dosages and methods of administration were considered eligible. To allow adequate time for treatment effects to manifest, trials were required to have a minimum duration of 6 months. The outcomes studied were fractures, BMD percentage change, quality of life, adverse events, withdrawals, and survival.

2.3 What was the search methodology and search date of the Cochrane Review?

The review authors searched for studies that had been published up to 5 May 2022 from Cochrane Cystic Fibrosis and Genetic Disorders Group's Cystic Fibrosis Trials Register along with PubMed, US National Institutes of Health Ongoing Trials Register (www.clinicaltrials.gov), and World Health Organization International Clinical Trials Registry Platform (trialsearch.who.int). They also searched the reference lists of the included studies and any pertinent systematic reviews to identify additional references to relevant trials.

2.4 What are the main results of the Cochrane review?

The review included nine clinical trials involving 385 (predominantly male) participants that met the predefined inclusion criteria. All the trials shared similar study designs, with intervention durations ranging from 6 to 24 months, and utilized similar outcome measures. Only two of the trials were deemed to have a low risk of bias for every domain. Eight of the trials exclusively enrolled adult participants, while one trial included both adults and children, with the latter group ranging in age from five to 18 years. This trial had a significant proportion of children, amounting to 113 out of 128 participants (88%). The trial sizes varied, ranging from as few as five participants to as many as 128 participants. A single trial evaluated 34 adults after undergoing lung transplantation. Two trials investigated the use of intravenous pamidronate, while two other trials examined the effectiveness of intravenous zoledronate. Oral alendronate was administered in four trials, and oral risedronate was given in one trial. In eight of these trials, participants were provided with additional calcium and vitamin D supplementation, and with additional vitamin D supplementation in one trial. The certainty of the evidence was assessed by Jeffery et al.1 using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach.