How should I evaluate and manage an older adult with possible fractures, hypercalcemia, and a high anion‑gap metabolic acidosis?

Evaluation and Management of Older Adults with Possible Fractures, Hypercalcemia, and High Anion-Gap Metabolic Acidosis

Immediately stabilize the metabolic acidosis and hypercalcemia while simultaneously evaluating for fractures, as the acidosis itself can worsen hypercalcemia by increasing calcium efflux from bone, and both conditions significantly increase morbidity and mortality in older adults. 1

Immediate Metabolic Stabilization

Address the High Anion-Gap Metabolic Acidosis First

• Identify the underlying cause using the mnemonic approach: lactic acidosis (sepsis, tissue hypoperfusion), ketoacidosis (diabetic, alcoholic), toxins (methanol, ethylene glycol, salicylates), uremia, or 5-oxoproline (chronic acetaminophen use) 2, 3, 4
• Check serum lactate, ketones, renal function, osmolar gap, and medication history (particularly chronic acetaminophen or antibiotics) to determine etiology 4, 5
• Treat the underlying cause aggressively: fluid resuscitation for lactic acidosis, insulin for diabetic ketoacidosis, alcohol infusion and dialysis for toxic ingestions 2
• Avoid aggressive bicarbonate therapy unless pH <7.1, as bicarbonate generates CO2 and may worsen outcomes in lactic acidosis 2

Manage Hypercalcemia Concurrently

• Recognize that metabolic acidosis directly worsens hypercalcemia by increasing calcium release from bone while impaired renal function decreases calcium excretion 1
• Correct the acidosis with sodium bicarbonate infusion if appropriate, as this can normalize ionized calcium even without improvement in renal function (correlation r = -0.93) 1
• Initiate aggressive IV hydration with normal saline to enhance renal calcium excretion
• Consider calcitonin or bisphosphonates for severe hypercalcemia (>14 mg/dL or symptomatic)

Fracture Evaluation Protocol

Clinical Assessment

• Obtain detailed history of the fall mechanism, pain location (hip/groin, spine, wrist, shoulder), ability to bear weight, and any neurological symptoms 6
• Perform focused physical examination looking for localized tenderness, deformity, ecchymosis, limited range of motion, and neurological deficits 7
• Assess for red flags: new neurological deficits, severe uncontrolled pain, hemodynamic instability, or signs of infection requiring emergency transfer 7

Imaging Strategy

• Start with plain radiographs of symptomatic areas, but recognize that initial X-rays can be falsely negative in up to 10% of hip fractures 6
• Order MRI within 2-3 days if hip/groin pain persists despite negative radiographs, as occult femoral neck fractures are common in older adults 6
• Obtain spine imaging (radiography or vertebral fracture assessment) to detect subclinical vertebral fractures, which are frequent in patients with metabolic bone disease and predict future fracture risk 8
• Do not pursue additional imaging if radiographic findings are conclusive and clinical picture is consistent with stable insufficiency fracture 7

Comprehensive Fracture Risk Assessment

Immediate Workup

• Order DXA scan of lumbar spine and hip to quantify bone mineral density 8, 7
• Obtain laboratory evaluation: serum calcium, albumin, phosphorus, creatinine, TSH, vitamin D, PTH (given hypercalcemia), ESR, and protein electrophoresis to identify secondary osteoporosis 8
• Calculate 10-year fracture risk using FRAX or similar validated tool, incorporating clinical risk factors (age, gender, BMI, prior fracture, family history, glucocorticoid use) 8

Fall Risk Evaluation

• Document fall history in the past year and perform functional tests (Timed Up and Go test) 8, 6
• Conduct multifactorial assessment: gait and balance, vision, postural blood pressure, medication review (polypharmacy), cognitive function, and home environment hazards 6

Pharmacological Management

Immediate Fracture Prevention

• Prescribe calcium 1,000-1,200 mg/day (dietary plus supplementation) combined with vitamin D 800 IU/day, which reduces non-vertebral fractures by 15-20% and falls by 20% 9, 7, 6
• However, temporarily hold calcium supplementation until hypercalcemia is corrected to avoid worsening the condition
• Initiate oral bisphosphonate therapy (alendronate or risedronate) once metabolic abnormalities are stabilized, as this reduces vertebral fractures by 47-48%, non-vertebral fractures by 26-53%, and hip fractures by 51% 7

Pain Management

• Use multimodal analgesia with acetaminophen as first-line, avoiding opioids due to increased risk of delirium, respiratory depression, and subsequent falls 6
• Note the paradox: if chronic acetaminophen contributed to 5-oxoproline acidosis, this must be discontinued 4, 5

Mobilization and Rehabilitation

Early Mobilization Protocol

• Allow weight-bearing as tolerated immediately with assistive device for most insufficiency fractures (pubic rami, stable vertebral compression fractures) 7, 6
• Initiate finger-motion exercises immediately after distal radius fracture casting/surgery to prevent edema and stiffness 9
• Begin shoulder, elbow, wrist, and hand ROM exercises within first postoperative days for shoulder fractures, avoiding overhead activities until radiographic healing 9
• Do not prescribe complete bed rest, as immobility increases complications including pneumonia, pressure ulcers, and deconditioning 6

Exercise Prescription

• Prescribe supervised exercise program including gait, balance, functional training, and resistance training at 3 sessions per week for at least 12 months 9, 6
• Combined muscle-strengthening and balance training reduces fall incidence by approximately 20% in older adults with osteoporosis 9
• Recommend ≥30 minutes of weight-bearing activity (walking or jogging) at least three times per week to improve bone mineral density 9

Organizational Structure

Fracture Liaison Service Referral

• Immediately refer to Fracture Liaison Service (FLS), which is the most effective organizational structure for secondary fracture prevention, increasing appropriate management from 26% to 45% within 6 months 8, 9, 6
• The FLS coordinator (specialized nurse under physician supervision) will organize diagnostic investigations, start interventions, and provide medical information to patient and primary care physician 8
• Secondary fracture risk is highest immediately after the index event and gradually decreases over time, making early intervention critical 8, 6

Special Considerations for This Complex Case

Metabolic Acidosis-Hypercalcemia-Fracture Nexus

• The metabolic acidosis may indicate underlying sepsis, renal failure, or toxic ingestion, all of which independently increase fall risk and fracture complications 2, 4
• Hypercalcemia suggests possible primary hyperparathyroidism or malignancy, which requires endocrine evaluation once acute issues are stabilized 1
• Chronic acidosis itself causes bone loss by increasing calcium efflux from bone, creating a vicious cycle with fracture risk 1

Monitoring and Follow-Up

• Perform repeat DXA scanning every 1-3 years, with earlier repeat (within 12 months) for patients with recent fragility fracture 9
• Monitor for treatment tolerance and medication adherence through systematic FLS follow-up 9
• Reassess fall risk and functional status at regular intervals, adjusting interventions as needed 6

Common Pitfalls to Avoid

• Do not delay fracture evaluation while focusing solely on metabolic abnormalities, as occult fractures can present with delayed symptoms 6
• Do not overlook subclinical vertebral fractures, which are present in many patients with metabolic bone disease and predict future fracture risk independent of BMD 8
• Do not assume normal X-rays exclude fracture in older adults with persistent localized pain—obtain MRI 6
• Do not prescribe calcium supplementation until hypercalcemia is corrected, as this will worsen the condition
• Do not use aggressive bicarbonate therapy for lactic acidosis unless pH <7.1, as this may worsen outcomes 2