One of the major
challenges of treatment of osteoporosis in patients with eGFR below 30
mL/minute is the limited available data. Bisphosphonates are usually not
advocated in this population since most agents have renal clearance and
patients were frequently excluded from clinical trials. Post-hoc analyses of
studies in postmenopausal women with grades 4 and 5 CKD and a definite
diagnosis of osteoporosis revealed efficacy and short-term safety of
bisphosphonates, denosumab, and raloxifene in addition to calcium and vitamin D
supplementation. Bisphosphonates demonstrated increase in BMD, and reduction in
vertebral fracture incidence regardless of degree of renal dysfunction. To
date, anti-osteoporotic agents have not been recommended in CKD stage 5D due to
lack of data on security and on its beneficial impact against fracture. Though
some small studies have reported an amelioration of BMD with these drugs in
Patients with severe renal impairment are at higher risk for hypercalcemia due to calcium and vitamin D supplements, or for hypocalcemia if taking denosumab therapy. Therefore, serum calcium, phosphorus, parathyroid hormone, 25-hydroxyvitamin D should be monitored at least every four months. Furthermore, renal function should be routinely measured in patients taking bisphosphonates. Markers of bone turnover, including but not limited to C terminal telopeptide (CTX), N terminal telopeptide (NTX), and pyridinolines (PYR) are metabolized and/or excreted renally, and will accumulate in renal dysfunction. Therefore, they should not be used to monitor response to therapy in patients with eGFR below 30 mL/minute. Despite neither predicting fracture risk nor the type of renal osteodysthrophy, bone densitometry of the hip and spine may be performed to monitor for changes in BMD. In complex patients, a bone biopsy should be considered prior to initiating osteoporosis treatment.
• For patients with low BMD (T-score below 2.5) associated with fragility fracture and grades 4 or 5 CKD, pharmacologic therapy might be considered after excluding all other CKD-related low BMD diagnoses.
• Adjusted dose of oral bisphophonates are typically recommended based on clinical experience and existing data.
• Intravenous (IV) bisphosphonates should be used as a last resort only in patients who cannot tolerate previous therapies and are at high risk for multiple fractures.
• Nephrotoxicity is a significant potential problem with IV bisphosphonates (Zoledronic acid). It is dependent on both dose and infusion rates.
• The patterns of nephrotoxicity from IV bisphosphonates include acute tubular necrosis and collapsing focal segmental glomerulosclerosis.
• Strict adherence to guidelines for monitoring renal function prior to each dose and temporarily withholding therapy in the setting of renal insufficiency, may help prevent nephrotoxicity from these agents. Denosumab can be an interesting alternative since it is not renally excreted. Further studies are required in patients with CKD.
• Medications that increase bone formation, such as teriparatide and anti-sclerostin monoclonal antibodies (romosozumab and blosozumab) seem to be promising alternatives for treating osteoporosis in CKD patients with low-turnover bone disease.
Sandra El Hajj, PharmD
Steven Gabardi, PharmD, BCPS, FCCP
Fellype Barreto, MD, PhD
Leonardo Riella, MD, PhD
1. Miller PD,Roux C, Boonen S, et al. Safety and efficacy of risedronate in patients withage-related reduced renal function as estimated by the Cockcroft and Gaultmethod: a pooled analysis of nine clinical trials. J Bone Miner Res 2005;20:2105
2. Jamal SA,Bauer DC, Ensrud KE, et al. Alendronate treatment in women with normal toseverely impaired renal function: an analysis of the fracture interventiontrial. J Bone Miner Res 2007; 22:503
3. Ishani A,Blackwell T, Jamal SA, et al. The effect of raloxifene treatment inpostmenopausal women with CKD. J Am Soc Nephrol 2008; 19:1430.
4. Jamal SA, Ljunggren O, Stehman-Breen C, et al.Effects of denosumab on fracture and bone mineral density by level of kidneyfunction. J Bone Miner Res 2011;26(8):182