TABLE 1.
Characteristics of randomized controlled trials evaluating effects of osteoporosis medications on patients diagnosed as having chronic kidney disease (CKD), receiving dialysis, or having undergone kidney transplantation.
| Study, year | Population | Location | Intervention | Comparison | Sample size (n) | Follow-up (months) | Selected outcomes | Main reported result(s) | Risk of bias | Funding source |
|---|---|---|---|---|---|---|---|---|---|---|
| Coco et al. (2003) | Adult men and women post-kidney transplantation | United States | IV pamidronate 60 mg within 48 h after transplantation followed by 30 mg at months 1, 2, 3, and 6 | Oral calcitriol and calcium carbonate | 59 | 12 | Vertebral and hip BMD, vertebral and hip fractures, renal events, hypocalcemia, hypercalcemia | Pamidronate was more effective in preserving vertebral BMD than treatment in compared groups | Moderate | Not reported |
| Hernandez et al., 2003 (Jamal et al., 2011) | Postmenopausal women >50 years old receiving dialysis | Venezuela | Oral raloxifene 60 mg daily | Placebo | 50 | 12 | Lumbar spine and femoral neck BMD | Raloxifene significantly improved lumbar spine BMD | Moderate | Industry and government |
| Jamal et al., 2007 (Torregrosa et al., 2010) | Postmenopausal women 55–80 years old, eGFR <45 ml/min | Multicenter, United States | Oral alendronate 5 mg daily | Placebo | 581 | 36 to 48 | Lumbar spine, femoral neck, and total hip BMD; clinical fractures and vertebral fractures; GI; CV; cerebrovascular events; cancer; death | Alendronate increased total hip BMD | Moderate | Government |
| Miller et al., 2007 (Jamal et al., 2007) | Postmenopausal women 42–86 years old, GFR 30–79 ml/min | Multicenter, multicountry | SC teriparatide 20 or 40 mcg daily | Placebo | 731 | Median, 21 | Lumbar spine and femoral neck BMD; vertebral and nonvertebral fractures; renal-related adverse events; hypercalcemia; gout; arthralgia | Teriparatide increased lumbar spine and femoral neck BMD. | Moderate | Industry |
| Incidence of vertebral and nonvertebral fractures was lower in patients treated with teriparatide | ||||||||||
| Ishani et al., 2008 (Miller et al., 2007) | Postmenopausal women 31–80 years old, CrCl <60 ml/min | Multicenter, multicountry | Oral raloxifene 60 or 120 mg daily | Placebo | 4,973 | 36 | Lumbar spine and femoral neck BMD; vertebral and non-vertebral fractures; renal and GI adverse events | Raloxifene treatment was associated with a large increase in spine BMD and a decrease in vertebral fractures | Moderate | Not reported |
| Walsh et al. (2009) | Post-kidney transplantation men and women 18–75 years old | Multicenter, United Kingdom | IV pamidronate 1 mg/kg at baseline and at 1, 4, 8, and 12 months after transplantation | Control (no bisphosphonates) | 93 | 24 | Lumbar spine, femoral neck, total hip, and Ward’s area BMD; fracture rate; hypocalcemia; and renal adverse events | Pamidronate increased the BMD of lumbar spine, total hip, and Ward’s area of the hip | Moderate | Industry |
| Toussaint et al. (2010) | Men and women 18–80 years old, GFR 20–60 ml/min/1.73 m2 and Clcr >25 ml/min | Single-center, Australia | Oral alendronate 70 mg weekly | Placebo | 50 | 18 | Lumbar spine and femoral neck BMD; vertebral and hip fracture; GI and renal adverse events; death | Alendronate increased lumbar spine BMD | Moderate | Industry |
| Torregrosa et al., 2010 (Marques et al., 2019) | Post-kidney transplantation men and women 18–75 years old | Multicenter, Spain | Oral risedronate 35 mg weekly | Oral vitamin D and calcium daily | 101 | 12 | Lumbar spine and femoral neck BMD; vertebral fracture; renal adverse events; hypercalcemia; hyperphosphatemia; dyspepsia; death | Risedronate increased lumbar spine BMD at 6- and 12-month follow-up and increased femoral neck BMD only at 6-month follow-up | Moderate | Industry |
| Jamal et al., 2011 (Ishani et al., 2008) | Postmenopausal women 60–90 years old, stage 3 or 4 CKD | Multicenter, multicountry | SC denosumab 60 mg every 6 months | Placebo | 2,890 | 36 | Lumbar spine, femoral neck, and total hip BMD; vertebral fractures; renal, CV, and infection-related adverse events | (Bikbov et al., 2020) Denosumab reduced the incidence of vertebral fractures over 36 months for patients with stage 3 CKD > | Moderate | Industry |
| (System URD, 2013) Denosumab increased lumbar spine BMD, femoral neck BMD, and total hip BMD over 36 months for patients with stage 3 CKD | ||||||||||
| (Tentori et al., 2014) Denosumab increased femoral neck BMD and total hip BMD over 36 months for patients with stage 4 CKD | ||||||||||
| Smerud et al., 2012 (Torregrosa et al., 2010) | Post-kidney transplantation women and men >18 years old | Single-center, Norway | IV Ibandronate 3 mg every 3 months | Placebo | 129 | 12 | Lumbar spine, total femur, ultradistal radius, proximal 1/3 radius, and total body BMD; vertebral fractures; renal adverse events; musculoskeletal pain; infections; death | Ibandronate significantly increased total femur and ultradistal radius BMD | Moderate | Industry |
| Haghverdi et al. (2014) | Postmenopausal women >40 years old, stage 5 CKD or hemodialysis | Single-center, Iran | Oral raloxifene 60 mg daily | Placebo | 51 | 8 | Lumbar spine and femoral neck BMD; vertebral fractures | Raloxifene significantly increased lumbar spine BMD | Moderate | Not reported |
| Sánchez-Escuredo et al., 2015 (Smerud et al., 2012) | Post-kidney transplantation women and men 50–75 years old | Single-center, Spain | Oral ibandronate 150 mg monthly | Oral risedronate 35 mg weekly | 69 | 12 | Lumbar spine and femoral neck BMD; GI and renal adverse events; death | Both monthly oral ibandronate and weekly oral risedronate increased lumbar spine BMD | Moderate | Not reported |
| Bonani et al., 2016 (17) | Post-kidney transplantation adult men and women | Single-center, Switzerland | SC denosumab 60 mg every 6 months | Control (no treatment) | 90 | 12 | Lumbar spine, femoral neck, and total hip BMD; fracture; renal and GI adverse events; musculoskeletal pain; hypocalcemia; hypercalcemia; infections; death | Denosumab increased total lumbar spine and total hip areal BMD | Moderate | University and university hospital |
| Shigematsu et al., 2017 (Torregrosa et al., 2010) | Men and women >40 years old with stage 3 CKD | Multicenter, Japan | Oral risedronate 2.5 mg once daily | Oral risedronate 17.5 mg once weekly or intermittent oral etidronate (one cycle: 2 weeks of 200 mg once daily followed by 10 weeks off) | 228 | 12–24 | Lumbar spine BMD, atypical femoral fractures, renal and GI adverse events, hypocalcemia, hypercalcemia, osteonecrosis of the jaw | Risedronate increased lumbar spine BMD | Moderate | Industry |
| Iseri et al., 2019 (Iseri et al., 2019) | Men and women >20 years old undergoing hemodialysis | Multicenter, Japan | SC denosumab 60 mg every 6 months | IV alendronate 900 mg every 4 weeks | 46 | 12 | Lumbar spine, femoral neck, and distal radius BMD; vertebral fracture; GI adverse events; musculoskeletal pain; hypocalcemia; hypercalcemia; infections; death | Denosumab and alendronate both significantly increased lumbar spine BMD | Moderate | Industry |
| Marques et al., 2019 (Bonani et al., 2016) | Post-kidney transplantation, ≥18 years old | Single-center, Brazil | IV zoledronate 5 mg once | Control (cholecalciferol) | 32 | 12 | Lumbar spine, femoral neck, and total hip BMD; renal adverse events; hypocalcemia; hypercalcemia | Zoledronate increased lumbar spine and total hip BMD | Moderate | Government |
| Sugimoto et al., 2019 (Sugimoto et al., 2019) | CKD stage G3 (eGFR ≥30 to <60 ml/min/1.73 m2), men >50 years old and women >50 years old ≧2 years after menopause | Multicenter, Japan | Oral risedronate 75 mg monthly | Oral calcium lactate daily | 41 | 12 | Lumbar spine BMD, incidence of adverse events | Lumbar spine BMD significantly increased from baseline at months 6 and 12 | Moderate | Industry |
Abbreviations: CKD, chronic kidney disease; BMD, bone mineral density; IV, intravenous; SC, subcutaneous; CV, cardiovascular; GI, gastrointestinal.