Is determining the degree of Chronic Kidney Disease (CKD) important before choosing osteoporosis treatment and are anabolic bone medications, such as Teriparatide (Teriparatide), an option for patients with CKD?

Determining CKD Stage is Critical Before Treating Osteoporosis, and Anabolic Agents Can Be Used in CKD with Important Caveats

Yes, determining the degree of CKD is essential before selecting osteoporosis treatment, as management strategies differ significantly across CKD stages, and anabolic bone medications like teriparatide are options for patients with CKD stages 3a-4, though their use requires careful consideration of bone turnover status and mineral metabolism. 1

Why CKD Stage Matters for Osteoporosis Treatment

The Complexity of Bone Disease in CKD

Patients with CKD face a dual bone disorder problem: traditional osteoporosis coexists with CKD-mineral and bone disorder (CKD-MBD), which involves abnormalities in calcium, phosphate, PTH, and vitamin D metabolism that directly affect bone turnover and quality. 2, 3 The type and severity of bone disease varies dramatically by CKD stage, making a one-size-fits-all approach dangerous. 1

Treatment decisions must be based on serial assessments of phosphate, calcium, and PTH levels considered together, not on single laboratory values or GFR alone. 1 This integrated approach recognizes that mineral metabolism disturbances interact with bone health in complex ways that change as kidney function declines. 3

Stage-Specific Treatment Approaches

CKD Stages 3a-3b (eGFR 30-59 mL/min)

• Osteoporosis medications can generally be used similarly to the general population in these stages. 1, 4
• BMD testing by DXA is recommended if results will impact treatment decisions, as hip BMD predicts fractures across CKD stages 3a-5D with similar accuracy to the general population. 1
• Bone biopsy is no longer a prerequisite for initiating antiresorptive therapies in CKD stage 3a-4, representing a major shift from previous guidelines. 1

CKD Stages 4-5 (eGFR <30 mL/min) and Dialysis (5D)

• The approach becomes more nuanced due to higher prevalence of abnormal bone turnover disorders, particularly adynamic bone disease. 1, 5, 4
• Treatment choices should account for the magnitude and reversibility of biochemical abnormalities (calcium, phosphate, PTH, alkaline phosphatase) and CKD progression. 2, 5
• Bone biopsy may be reasonable if knowledge of renal osteodystrophy type will impact treatment decisions, though it is not routinely required. 1

Anabolic Bone Medications in CKD: Teriparatide

Evidence for Efficacy

Teriparatide ranked highest for improving vertebral BMD in network meta-analysis of CKD patients (SUCRA = 97.8%) and was associated with significantly reduced fracture risk compared to placebo (OR 0.19,95% CI 0.10-0.35). 6 This makes it one of the most effective options for preventing bone loss in CKD patients. 6

Safety Considerations by CKD Stage

Pharmacokinetics in Renal Impairment

In patients with severe renal impairment (CrCl <30 mL/min), teriparatide AUC and half-life increase by 73% and 77% respectively, though maximum serum concentration remains unchanged. 7 The FDA label notes it is unknown whether teriparatide alters the underlying metabolic bone disease in chronic renal impairment. 7

Calcium Metabolism Concerns

• Teriparatide transiently increases serum calcium, with peak levels occurring 4-6 hours post-dose and returning to baseline by 16-24 hours. 7
• In CKD patients, where calcium homeostasis is already disrupted, this transient hypercalcemia requires careful monitoring, particularly when combined with calcium supplements or active vitamin D. 2, 3, 7
• The guideline recommends avoiding hypercalcemia in all CKD stages (2C recommendation). 1

Clinical Use Algorithm for Teriparatide in CKD

For CKD stages 3a-4:

• Can be used if BMD testing shows low bone density and fracture risk is high 1
• Monitor serum calcium 4-6 hours post-dose initially, then periodically 7
• Adjust calcium supplementation downward if needed 7
• Track trends in phosphate, calcium, and PTH together 1

For CKD stages 5-5D:

• Evidence is limited but teriparatide may slightly improve lumbar spine BMD 8
• Consider bone biopsy if concern exists for adynamic bone disease (low turnover state), as anabolic agents work best with adequate bone turnover 1, 5, 4
• Very close calcium monitoring is essential given altered mineral metabolism 2, 3
• Coordinate with nephrology regarding phosphate binders and vitamin D analogs 2, 3

Alternative Anabolic and Antiresorptive Options

Denosumab

Denosumab ranked highest for improving femoral neck BMD (SUCRA = 88.3%) and significantly reduced fracture risk (OR 0.40,95% CI 0.27-0.58) in CKD patients. 6 However, it carries substantial risk of hypocalcemia in advanced CKD and requires concomitant active vitamin D administration with careful calcium monitoring. 4

Bisphosphonates

Bisphosphonates can be used in CKD stages 3a-3b, but require caution in stage 4 and beyond due to concerns about adynamic bone disease and accumulation. 5, 4 Oral bisphosphonates appear safer than intravenous formulations in lower creatinine clearance. 5

Raloxifene

Raloxifene may prevent vertebral fractures (OR 0.52,95% CI 0.41-0.67) but effects on BMD are inconsistent. 6, 8 It should be used with caution in postmenopausal women with CKD. 4

Critical Pitfalls to Avoid

The "Renalism" Trap

Withholding bone drugs solely based on GFR cutoffs without considering the full clinical picture may constitute discrimination and widen the treatment gap in osteoporosis. 9 The decision should integrate CKD stage, mineral metabolism parameters, bone turnover assessment, and fracture risk. 9

The Bone Turnover Dogma

The concept of choosing between antiresorptive or anabolic drugs based solely on pre-treatment bone turnover assessment (via biomarkers or biopsy) requires critical re-evaluation, as no biomarker combination robustly diagnoses turnover status in individual patients. 1, 9 PTH trends are more useful than single values, but even PTH assays vary significantly across studies. 1

Ignoring Mineral Metabolism

Treating osteoporosis without addressing elevated phosphate, abnormal calcium, or PTH disturbances leads to unintended consequences. 1 For example, vitamin D therapy can cause hypercalcemia when phosphate is uncontrolled. 3 The 2017 KDIGO guidelines emphasize that treatments should be based on serial assessments of all three parameters together. 1

Calcium-Based Phosphate Binders

Using calcium-based phosphate binders in patients with low PTH or severe vascular calcification worsens extraskeletal calcification. 3 Non-calcium-based binders like sevelamer are preferred in stage 5 patients, particularly those with these risk factors. 3

Practical Management Framework

Step 1: Determine CKD stage and assess mineral metabolism

• Measure calcium, phosphate, PTH, alkaline phosphatase, and 25-hydroxyvitamin D 2
• Frequency varies by stage: every 3 months for stage 4, monthly initially then every 3 months for stage 5 3

Step 2: Perform BMD testing if results will change management

• DXA predicts fractures reliably across CKD stages 3a-5D 1
• Consider bone biopsy only if renal osteodystrophy type would alter treatment choice 1

Step 3: Optimize mineral metabolism before or concurrent with osteoporosis treatment

• Lower elevated phosphate toward normal range 1
• Avoid hypercalcemia 1
• Treat progressively rising or persistently elevated PTH (not single values) 2, 3

Step 4: Select osteoporosis medication based on CKD stage and bone turnover

• Stages 3a-4: Teriparatide or denosumab are most effective; bisphosphonates and raloxifene are alternatives 6, 8
• Stages 5-5D: Limited evidence; consider teriparatide with close monitoring or denosumab with mandatory calcium/vitamin D supplementation 8, 4
• If concern for low turnover exists, bone biopsy may guide choice away from antiresorptives 1, 5

Step 5: Monitor response and safety

• Serial calcium measurements, especially 4-6 hours post-dose with teriparatide 7
• Continue tracking phosphate, calcium, PTH trends together 1
• Reassess BMD and adjust therapy as kidney function changes 2