Monitoring:
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.
Recommendations:
• 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
Additional References:
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