Bisphosphonates for the Treatment of Osteoporosis In Chronic Kidney Disease: an Individual Patient Level Systematic Review and Meta-Analyses

Bisphosphonates for the Treatment of Osteoporosis In Chronic Kidney Disease: an Individual Patient Level Systematic Review and Meta-Analyses

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Kidney disease is public health concern that affects 10-15% of the population that is driven by aging, diabetes, and high blood pressure. Kidney disease including dialysis is associated with an increased risk of fractures due an underlying bone disease caused by kidney disease itself referred to as the “mineral bone disorder.” Osteoporosis (OP) is a common bone disease that is due to a structural abnormality related to a decrease in bone density that can also contribute to fractures. aging is a shared risk factor for both OP and kidney disease with an overlap between these conditions. However, the extent of OP in individuals with kidney disease is uncertain using bone mineral density (BMD) testing to diagnose is not reliable due to interference by calcium deposition but it is thought to frequently coexist in the elderly with kidney disease. In the general population, ”bisphosphonates” are a class of medication that increase BMD in different skeletal sites (hip, spine, wrist etc.) and prevent fractures at these sites. However, how well these medcations work and their safety profiles in the setting of kidney disease is uncertain. This is because patients with kidney dysfunction have been systematically excluded from studies of these drugs as they are dosed based on kidney function. Bisphosphonates are also associated with adverse events including different types of kidney injury and bone related complications which may be modified by the presence of underlying kidney disease. Thus, these drugs have yet to be fully studied in the kidney disease population although they are frequently used off-label in special circumstances. Further research needs to be done to improve the outcomes of patients with kidney disease and OP. The goal of this study is to perform a systematic review and meta-analysis of previous clinical trials of bisphosphonates compared to placebo which have included a number of patients with kidney disease. We want to compare the subgroup of participants with kidney dysfunction and this requires individual patient level data to identify kidney dysfunction using formulas that include demographic information (age, sex, race) and laboratory tests of kidney function. The objective is to see if there are any differences in the outcomes of patients with or without kidney diseases across the different types of bisphosphonates. We have already identified 38 studies that meet the inclusion criteria into our study including 8 bisphosphontes (alendronate, risedroante, etidronate, minodronate, tiludronate, ibandronate, zoledronic acid , clodronate) and are at the point of collecting data from individual studies.

[{ "PostingID": 2215, "Title": "ROCHE-MF4411", "Description": "Multicenter, double-blind, placebo-controlled, randomized study on the efficacy and safety of ibandronate over 3 years in patients with postmenopausal osteoporosis using a continuous oral and an intermittent oral dosing regimen.

Medicine: ibandronate, Condition: osteoporosis with pathological fracture, Phase: 3, Clinical Study ID: MF4411, Sponsor: Roche" },{ "PostingID": 2216, "Title": "ROCHE-MF4380", "Description": "Efficacy and safety of long-term, intermittent iv ibandronate treatment in women with postmenopausal osteoporosis.

Medicine: ibandronate, Condition: osteoporosis with pathological fracture, Phase: 3, Clinical Study ID: MF4380, Sponsor: Roche" },{ "PostingID": 3441, "Title": "GSK-BON103593", "Description": "A one year, parallel, placebo-controlled, double-blind, randomized study to assess the effect of monthly 150mg oral ibandronate dosing versus placebo on bone quality and strength at the proximal femur in women with osteoporosis" },{ "PostingID": 4189, "Title": "NOVARTIS-CZOL446H2310", "Description": "Multinational, multicenter, double-blind, randomized, placebo-controlled, parallel group study assessing the efficacy of intravenous zoledronic acid in preventing subsequent osteoporotic fractures after a hip fracture" },{ "PostingID": 4190, "Title": "NOVARTIS-CZOL446H2301", "Description": "A multicenter, double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of zoledronic acid in the treatment of osteoporosis in postmenopausal women taking cal-cium and vitamin D" },{ "PostingID": 4195, "Title": "NOVARTIS-CZOL446M2309", "Description": "A Two Year Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Fracture Efficacy and Safety of Intravenous Zoledronic Acid 5 mg Annually for the Treatment of Osteoporosis in Men" },{ "PostingID": 4676, "Title": "ROCHE-BA18492", "Description": "Double-blind, Placebo-controlled, Randomized, Multicenter Study to Assess the Efficacy and Safety of Oral Ibandronate Once Monthly in Postmenopausal Women With Osteopenia 

Medicine: Ibandronate, Condition: osteoporosis with pathological fracture, Phase: 4, Clinical Study ID: BA18492, Sponsor: Roche" },{ "PostingID": 4677, "Title": "ROCHE-MF4433", "Description": "Double-blind, placebo controlled, randomized study on the efficacy and safety of ibandronate during 2 years treatment in patients with postmenopausal osteoporosis using a continuous oral (0.5mg daily) and in intermittent oral (20mg every 2nd day for 24 days every 3 months) regimen.

Medicine: Ibandronate, Condition: osteoporosis with pathological fracture, Phase: 2, Clinical Study ID: MF4433, Sponsor: Roche" },{ "PostingID": 4678, "Title": "ROCHE-MF4470", "Description": "Multicenter, double blind, placebo-controlled, randomized, dose-finding study on the efficacy and safety of ibandronate (BM 21.0955) during 2 years treatment in patients with postmenopausal osteoporosis using an intermittent (every 3 months) i.v. injection of 1 mg or 2 mg.

Medicine: Ibandronate, Condition: osteoporosis with pathological fracture, Phase: 2, Clinical Study ID: MF4470, Sponsor: Roche" },{ "PostingID": 4679, "Title": "ROCHE-MF4488", "Description": "Multicenter, double-blind, placebo-controlled, randomized dose-finding study on the efficacy and safety of ibandronate during 2 years treatment in potmenopausal women for prevention of postmenopausal bone loss using an intermittent i.v. bolus injection of 0.5, 1.0 and 2.0 mg regimen every three months

Medicine: Ibandronate, Condition: osteoporosis with pathological fracture, Phase: 2/3, Clinical Study ID: MF4488, Sponsor: Roche" },{ "PostingID": 4753, "Title": "NOVARTIS-CZOL446N2312", "Description": "A 2-year Randomized, Multicenter, Double-blind, Placebo-controlled Study to Determine the Efficacy and Safety of Intravenous Zoledronic Acid 5 mg Administered Either Annually at Randomization and 12 Months, or Administered at Randomization Only in the Prevention of Bone Loss in Postmenopausal Women With Osteopenia" }]

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. Canadian Journal of Kidney Health and Disease. 2024;11.
DOI: 10.1177/20543581241283523