What is the appropriate management for a patient with hip pain that worsens at night and improves with walking, elevated alkaline phosphatase (AP) level, and suspected bone pathology?

Management of Hip Pain with Nocturnal Worsening, Improvement with Walking, and Elevated Alkaline Phosphatase

Begin with plain radiographs (AP pelvis and lateral hip views) as the initial imaging study, and measure serum alkaline phosphatase, calcium, phosphate, and 25-OH vitamin D levels to differentiate between Paget's disease, bone malignancy, and osteomalacia. 1

Initial Diagnostic Workup

Imaging Strategy

• Obtain AP pelvis radiographs plus lateral hip views (cross-table, frog-leg, or Dunn) as the first-line imaging modality for all patients with chronic hip pain, as radiographs can identify Paget's disease, primary bone tumors, metastatic disease, and other osseous pathology 1
• Radiographs serve as an excellent screening tool and guide selection of additional imaging techniques if initial films are negative or equivocal 1

Laboratory Evaluation

• Measure serum alkaline phosphatase (AP), calcium, phosphate, and 25-OH vitamin D3 levels to distinguish metabolic bone disease from malignancy 1, 2
• Elevated AP with normal bilirubin strongly suggests bone pathology rather than hepatobiliary disease 3
• Check lactate dehydrogenase (LDH) as it has prognostic value in osteosarcoma and bone malignancies 1

Clinical Pattern Recognition

Night Pain That Improves with Walking

This specific pattern is highly characteristic of:

• Paget's disease of bone - presents with insidious, constant pain that is non-mechanical in nature and often present at night 1
• Bone malignancy (osteosarcoma) - 75% arise around the knee but can affect the hip, with pain beginning insidiously and becoming constant, present at night 1
• Osteomalacia - causes dull localized or generalized bone pain with muscle weakness 2

Elevated Alkaline Phosphatase Interpretation

• AP levels at least twice the upper limit of normal suggest Paget's disease and warrant treatment consideration 1, 4
• Extremely high AP (>1,000 U/L) in hospitalized patients most commonly indicates sepsis, malignant obstruction, or bone involvement from malignancy/Paget's disease 3
• Elevated AP with reduced serum phosphate and/or low 25-OH vitamin D3 indicates osteomalacia 2

Algorithmic Approach Based on Initial Findings

If Radiographs Show Paget's Disease

• Treat with bisphosphonates (alendronate 40 mg once daily for 6 months) if AP is at least twice the upper limit of normal, as this achieves normalization or >60% reduction in AP in approximately 85% of patients 5
• Monitor serum AP periodically after treatment; consider re-treatment if relapse occurs based on rising AP levels 5
• Bisphosphonates relieve bone pain, decrease biochemical markers, and may prevent complications if used early 4

If Radiographs Show Lytic Lesions or Bone Destruction

• Suspect primary bone malignancy (osteosarcoma, Ewing sarcoma) or metastatic disease 1
• Obtain tissue biopsy with sufficient material for histology, immunohistochemistry, molecular pathology, and biobanking 1
• For suspected Ewing sarcoma, EWS translocation detection by RT-PCR (frozen tissue) or FISH (paraffin-embedded tissue) is mandatory 1
• Refer immediately to multidisciplinary tumor board including orthopedic oncology, medical oncology, radiology, and pathology 1

If Radiographs Are Negative or Equivocal

• Proceed to MRI without contrast or bone scintigraphy to detect occult bone pathology 1
• MRI is highly sensitive and specific for detecting osseous and soft tissue abnormalities and should be the first advanced imaging after radiographs 1
• Consider technetium Tc-99m bone scan or 18F-fluoride PET to identify areas of active bone turnover, particularly useful for detecting multifocal Paget's disease or metastatic disease 1

If Hypophosphatemia Is Present

• Suspect oncogenic osteomalacia (tumor-induced osteomalacia) when elevated AP occurs with hypophosphatemia, bone pain, and pathological fractures 6
• Perform CT and MRI imaging to identify phosphaturic mesenchymal tumors, which are often small and difficult to locate 6
• Tumor excision leads to cure in most cases of oncogenic osteomalacia 2
• If no tumor identified, treat with phosphate supplementation for renal phosphate wasting syndromes 2

If Vitamin D Deficiency Is Present

• Treat with vitamin D and calcium supplementation (oral or parenteral if malabsorption present) 2
• Consider iliac crest bone biopsy to confirm osteomalacia if diagnosis remains uncertain, showing reduced mineralization of newly synthesized extracellular matrix 2

Critical Pitfalls to Avoid

• Do not assume elevated AP is hepatobiliary without checking fractionation or imaging - bone pathology with normal bilirubin is common 3
• Do not delay biopsy in suspected malignancy - delays in diagnosis increase mortality, complication rates, and hospital length of stay 1
• Do not overlook small phosphaturic tumors - they can cause severe osteomalacia with pathological fractures and require extensive imaging to locate 6
• Do not treat Paget's disease if asymptomatic with normal AP - treatment is reserved for symptomatic patients or those with AP at least twice normal 4

Supplementation Requirements

• Ensure adequate calcium and vitamin D supplementation regardless of underlying diagnosis, as deficiency can coexist with other bone pathology 5
• Patients over 70 years, nursing home-bound, or chronically ill require vitamin D supplementation due to increased insufficiency risk 5