Chronic kidney disease (CKD) is associated with an increased risk of bone fractures, as well as morbidity and mortality due to CKD-related bone mineral disorders. Osteopenia and osteoporosis are common in the general population and can increase the risk of spinal and non-spinal fractures (hip, radius, and others), as well as related morbidity and mortality.
The efficacy and safety of bisphosphonate therapy for the treatment of osteoporosis and osteopenia in CKD have been studied in a systematic review and individual patient meta-analysis with the aim of determining the effects of bisphosphonate therapy on fractures, bone mineral density (BMD), and side effects in adults across the spectrum of CKD and dialysis.
Clinical trial data were searched from Ageline, CINAHL, Cochrane Library, EMBASE, and Medline from inception to August 25, 2016, and supplemented with manual screening and clinicalstudydatarequest.com. The clinical trial data analyzed were from randomized placebo-controlled trials with 100 or more participants evaluating the treatment of primary osteoporosis/osteopenia in adult men and women with bisphosphonate therapy.
Characteristics, quality, and study data were independently assessed by two reviewers. The outcomes measured were fractures, BMD, and adverse events including decreased glomerular filtration rate (eGFR) and hypocalcemia (calcium <2.00 mmol/L). Of the 39 eligible studies, individual patient-level data were available for 7 studies, all of which were ibandronate studies. Of the 7,428 participants (5,010 patients with ibandronate, 2,418 patients with placebo), 100% were female, 98.6% were white, the mean body mass index was 25.7 kg/m² (SD 3.9), 18.9% were smokers, and there were 740 fracture events. The mean eGFR was 69.1 mL/min/1.73 m² (SD 15.9), including 14.5%, 54.9%, 27.5%, 3.0%, and 0.2% of patients with CKD stage G1, G2, G3A, G3B, and G4, respectively.
The results showed that compared with placebo, ibandronate therapy increased BMD in the hip (β 0.01493, SE 0.00166, p < 0.0001) and lumbar spine (β 0.02451, SE 0.002533, p < 0.0001). There was no difference in efficacy between PGK subgroups for hip BMD, but there was an increase in efficacy for lumbar spine BMD in the G4 PGK subgroup (β 0.2043, SE 0.04468, p < 0.0001).
Ibandronate reduces the risk of fracture in the overall population (HR 0.871, 95% CI 0.746-1.018), but there is no significant difference across PGK subgroups, except in patients with stage G3B PGK. this drug increased the risk of fracture (HR 3.862, 95% CI 1.156-12.903, interaction test p < 0.05). PGK stage (G2, G3A, G3B vs G1) and eGFR were not associated with fracture in either participants receiving bisphosphonate therapy or those treated with placebo. Ibandronate did not affect eGFR over 12 months, but increased the risk of hypocalcemia (HR 1.324, 95% CI 1.056-1.660) with no evidence of effect modification based on CKD stage (all interaction tests p > 0.05).
Conclusion:
This study found that chronic kidney disease does not alter the benefits of ibandronate in increasing hip and spine BMD at one year in adult women with osteoporosis or osteopenia, and that ibandronate is safe from a renal perspective.
Image: Illustration (Source: jcomp-Freepik)
Reference:
Whitlock R, MacDonald K, Tangri N, Walsh M, Collister D. The efficacy and safety of bisphosphonate therapy for osteopenia/osteoporosis in patients with chronic kidney disease: a systematic review and individual patient-level meta-analysis of placebo-controlled randomized trials. Can J Kidney Health Dis. 2024 Oct 8:11:20543581241283523. doi: 10.1177/20543581241283523.
