What should an orthopedic surgeon do when evaluating and treating a patient with multiple myeloma, including pre‑operative work‑up, surgical fixation options, anti‑resorptive therapy, and postoperative care?

Multiple Myeloma for the Orthopedic Surgeon

Orthopedic surgeons managing multiple myeloma patients should prioritize bone-modifying agents to prevent fractures, use arthroplasty over internal fixation for femoral pathologic fractures, and coordinate with radiation oncology for postoperative treatment to optimize function and survival. 1

Pre-operative Work-up and Risk Assessment

When evaluating a myeloma patient with bone lesions, focus your assessment on:

• Imaging requirements: Obtain complete femoral imaging (entire bone) to identify additional lesions that may require simultaneous treatment 1
• Renal function: Check serum creatinine and creatinine clearance before any bone-modifying agent administration, as myeloma patients frequently have renal impairment 2
• Calcium and vitamin D status: Assess and correct deficiencies before surgery, as hypocalcemia is common with bone-modifying agents 2
• Dental evaluation: Complete comprehensive dental examination before initiating bone-modifying therapy to prevent osteonecrosis of the jaw (ONJ) 2

The presence of a surgical indication itself signals worse prognosis—patients requiring surgery have significantly shorter survival (42-58 months) compared to those managed medically without surgical indication (62 months) 3. However, operating on indicated patients improves outcomes compared to not operating (58 vs 42 months survival) 3.

Bone-Modifying Agents: Critical for Fracture Prevention

Initiate bone-modifying agents in all myeloma patients with bone disease to reduce fracture incidence, regardless of whether surgery is planned. 1

Agent Selection and Dosing

For patients with normal renal function (creatinine clearance ≥30 mL/min):

• Zoledronic acid 4 mg IV over ≥15 minutes every 4 weeks, OR
• Denosumab 120 mg subcutaneously every 4 weeks 2

For patients with severe renal impairment (creatinine >3.0 mg/dL or clearance <30 mL/min):

• Pamidronate 90 mg IV over 4-6 hours (consider dose reduction) 2
• Denosumab is preferred as it requires no renal dose adjustment and has fewer renal adverse events 2

Critical pitfall: Never infuse pamidronate in <2 hours or zoledronic acid in <15 minutes—this increases renal toxicity risk 2.

Duration and Monitoring

• Continue bone-modifying therapy for up to 2 years 2
• For stable/responsive disease on maintenance therapy, consider extending dosing intervals to every 3 months 2
• Resume therapy upon relapse with new skeletal-related events 2
• Never abruptly stop denosumab—its reversible mechanism requires continuation or transition to bisphosphonates 2

Monitoring protocol:

• Serum creatinine before each bisphosphonate dose 2
• Serum calcium regularly (hypocalcemia more pronounced with denosumab) 2
• Spot urine for albuminuria every 3-6 months; if positive, obtain 24-hour collection 2
• Withhold bisphosphonates if creatinine rises without other cause; resume when within 10% of baseline 2

Surgical Fixation Strategy

Femoral Lesions: Arthroplasty Over Internal Fixation

For pathologic fractures of the proximal femur, perform arthroplasty (hemiarthroplasty or total hip arthroplasty) rather than internal fixation. 1 This recommendation is based on superior functional outcomes and reduced need for postoperative radiation therapy.

The AAOS/MSTS/ASCO/ASTRO consensus specifically recommends arthroplasty to:

• Improve patient function
• Decrease need for postoperative radiation
• Provide definitive, load-stable reconstruction 1

Surgical principles 4, 5:

• Aim for a final, load-stable solution that accounts for potentially long disease course (modern therapies extend survival significantly)
• Use hybrid stabilization combining bone cement with implants for diaphyseal lesions
• Consider modular tumor prosthesis systems for extensive proximal femoral involvement
• Perform en-bloc resection of involved bone segments when feasible

Spine Surgery Approach

For vertebral involvement, tailor the approach to severity 4, 5:

Minimally invasive options (for stable compression fractures without neurologic deficit):

• Kyphoplasty or vertebroplasty for pain control and height restoration

Open procedures (for instability or neurologic compromise):

• Selective decompression for isolated neural compression
• Dorsal spinal fusion for instability
• Vertebral body replacement for extensive destruction with instability

Absolute indications for spinal surgery 4:

• Progressive neurological deficits (8-10% of myeloma patients develop these)
• Spinal instability with mechanical pain
• Intractable pain despite conservative management

Radiation Therapy Integration

Coordinate with radiation oncology for postoperative treatment planning. 1 The expert panel recommends radiation therapy to:

• Decrease fracture rates in at-risk lesions
• Provide local tumor control postoperatively
• Reduce pain in unresectable lesions

Arthroplasty reduces the need for postoperative radiation compared to internal fixation, but radiation should still be considered based on residual disease burden 1.

Postoperative Management

Immediate Postoperative Care

• Early mobilization: The goal of surgery is immediate weight-bearing and function restoration 4, 6
• Continue bone-modifying agents: Do not interrupt therapy perioperatively unless renal function deteriorates 2
• Monitor for complications: Myeloma patients have high complication rates including periprosthetic fractures (18.75% in one series) and heterotopic ossification (25%) 7

Long-term Surveillance

• 1-year mortality: 53.3% in surgical patients 7
• 5-year mortality: 73.3% in surgical patients 7
• These sobering statistics underscore the importance of realistic goal-setting with patients and families

ONJ Prevention Strategy

Before any bone-modifying therapy 2:

• Complete dental examination and preventive dentistry
• Treat active oral infections
• Eliminate high-risk sites

During therapy:

• Maintain excellent oral hygiene
• Avoid invasive dental procedures when possible
• If dental work is necessary, coordinate timing with oncology team

Key Algorithmic Approach

1. Diagnosis confirmed → Immediate dental evaluation + baseline renal function
2. Initiate bone-modifying agent → Zoledronic acid/denosumab (normal renal function) OR pamidronate (impaired renal function)
3. Pathologic fracture occurs → Proximal femur: arthroplasty; Diaphysis: hybrid fixation with cement; Spine: based on stability/neurology
4. Postoperative → Early mobilization + continue bone-modifying agents + coordinate radiation therapy
5. Long-term → Monitor renal function, calcium, and albuminuria; continue therapy up to 2 years or until stable disease allows interval extension

The fundamental principle: Myeloma bone disease requires aggressive multidisciplinary management where orthopedic surgery provides definitive mechanical stability, bone-modifying agents prevent future events, and radiation provides local tumor control—all aimed at maximizing the patient's functional independence during their extended but ultimately limited survival 1, 4, 6.