Table 5.

Suggested directions for potential future research in patients with CKD 4–5D who are at high risk of fracture

	Osteoporosis drug	Research question	Key outcomes	Secondary outcomes
CKD stage 4	Bisphosphonates Denosumab	Is the efficacy of bisphosphonate therapy influenced by maintenance of serum PTH, 25(OH)vitamin D and phosphate to target ranges?	Fracture incidence Percentage change in BMD DXA derived TBS, HSA Measures of bone quality (HR-pQCT, bone biopsies)	Laboratory parameters: renal function PTH, calcium/phosphate FGF-23 Bone turnover markers (bALP)
CKD stage 4	Bisphosphonates	Safety and efficacy of limiting treatment duration (2 years), halving the dose or reducing frequency of dosing interval?	Adverse events, Fracture incidence Percentage change in BMD DXA derived TBS, HSA Measures of bone quality (HR-pQCT, bone biopsies)	Laboratory parameters: renal function PTH, calcium/phosphate FGF-23 Bone turnover markers (bALP)
CKD stage 4	Anabolic agents: Teriparatide Abaloparatide Romosozumab	Safety and efficacy of anabolic agents following control of CKD-MBD?	Adverse events, Fracture incidence Percentage change in BMD DXA derived TBS, HSA Measures of bone quality (HR-pQCT, bone biopsies)	Laboratory parameters: renal function PTH, calcium/phosphate FGF-23 Bone turnover markers (bALP)
CKD stage 5/5D	Bisphosphonates	Safety and efficacy of bisphosphonates in low bone turnover? What dose, length of treatment, dosing interval? Percent clearance by the dialysis membrane?	Adverse events Fracture incidence Percentage change in BMD DXA derived TBS, HSA Measures of bone quality (HR-pQCT, bone biopsies) Progression of vascular calcification	Laboratory parameters: PTH, calcium/phosphate FGF-23 Bone turnover markers (bALP)
CKD stage 5/5D	Denosumab	Is the efficacy of denosumab therapy influenced by maintenance of serum PTH, 25(OH)vitamin D and phosphate to target ranges?	Adverse events Fracture incidence Percentage change in BMD DXA derived TBS, HSA Measures of bone quality (HR-pQCT, bone biopsies) Progression of vascular calcification	Laboratory parameters: PTH, calcium/phosphate FGF-23 Bone turnover markers (bALP)
CKD stage 5/5D	Anabolic agents: Teriparatide Abaloparatide Romosozumab	Safety and efficacy following control of CKD-MBD? And in low bone turnover?	Adverse events Fracture incidence Percentage Change in BMD DXA derived TBS, HSA Measures of bone quality (HR-pQCT, bone biopsies) Progression of vascular calcification	Laboratory parameters: PTH, calcium/phosphate FGF-23 Bone turnover markers (bALP)
CKD 4–5D	Sequential treatment denosumab followed by bisphosphonate teriparatide followed by bisphosphonate or denosumab	Safety and efficacy of sequential treatment in patients with CKD-MBD?	Adverse events Fracture incidence Percentage change in BMD DXA derived TBS, HSA Measures of bone quality (HR-pQCT, bone biopsies) Progression of vascular calcification	Laboratory parameters: TH, calcium/phosphate FGF-23 Bone turnover markers (bALP)