What are the likely etiologies and initial work‑up for progressive diffuse musculoskeletal pain, fatigue, and anxiety in a 50‑year‑old woman who underwent surgical menopause three years ago and has a family history of Paget’s disease of bone?

Differential Diagnosis and Initial Work-Up for Progressive Diffuse Pain in Post-Surgical Menopause

This 50-year-old woman with surgical menopause, progressive diffuse pain, fatigue, and anxiety requires immediate evaluation for osteoporosis-related complications and exclusion of Paget's disease given the family history, followed by assessment for fibromyalgia and other systemic conditions.

Immediate Priority: Bone Health Assessment

Given the surgical menopause three years ago, this patient is at significantly elevated risk for osteoporosis and should undergo immediate bone density evaluation with DEXA scan 1. Women with early-induced menopause from oophorectomy experience accelerated bone loss and higher risk of insufficiency fractures 1.

Key Laboratory Studies to Order Now:

• Serum alkaline phosphatase (elevated in Paget's disease, typically >120 U/L) 2, 3, 4
• 25-hydroxy-vitamin D level (low in osteomalacia, which presents with generalized bone pain and muscle weakness) 1
• Serum calcium and phosphate (abnormal in metabolic bone disease) 1
• Parathyroid hormone (elevated in osteomalacia) 1
• ESR and CRP (elevated in inflammatory conditions, chronic non-bacterial osteitis, or occult malignancy) 1
• Complete blood count (anemia may suggest malignancy or chronic disease) 1

Evaluating for Paget's Disease

The family history of Paget's disease is a critical red flag 2. Approximately 15% of Paget's patients have a positive family history with autosomal dominant inheritance pattern 2, 3.

Specific Features to Assess:

• Age consideration: Paget's disease typically presents after age 50, making this patient's age appropriate for disease onset 2, 4
• Pain pattern: Bone pain is the most common symptom in Paget's disease 5, 4
• Skeletal sites: Most commonly affects pelvis, spine, skull, and long bones 3, 4
• If alkaline phosphatase is elevated: Obtain plain radiographs of symptomatic areas looking for mixed lytic-sclerotic lesions, cortical thickening, and bone enlargement 3, 5, 4
• Nuclear bone scan: Most sensitive test to define extent of disease if Paget's is suspected 3, 4

Excluding Other Critical Diagnoses

Metastatic Disease or Primary Bone Malignancy

Night pain is a red flag requiring urgent investigation for malignancy 1. In patients over 40 with bone pain, metastatic carcinoma is more common than primary bone tumors 1.

• Obtain plain radiographs of most symptomatic sites looking for bone destruction, new bone formation, or soft tissue swelling 1
• Consider whole-body imaging (CT chest/abdomen/pelvis or whole-body MRI) if constitutional symptoms, unexplained weight loss, or persistently elevated inflammatory markers 1
• Myeloma screen (serum protein electrophoresis, immunofixation, free light chains) given age and diffuse pain 1

Osteomalacia

This diagnosis must be excluded as it presents with generalized bone pain, muscle weakness, and elevated alkaline phosphatase 1.

• Low 25-hydroxy-vitamin D (<20 ng/mL)
• Low serum phosphate
• Elevated parathyroid hormone
• Bone demineralization on imaging 1

Chronic Non-Bacterial Osteitis (CNO)

While less common in this age group, CNO can present with multifocal bone pain 1. Consider if:

• Bone marrow edema on MRI at typical sites (anterior chest wall, spine, mandible)
• Elevated inflammatory markers
• Exclusion of infection and malignancy 1

Addressing Post-Menopausal Symptoms

Surgical menopause often causes more severe vasomotor symptoms than natural menopause, with negative impacts on quality of life, sleep, and mood 1. The anxiety and fatigue may be partially attributable to menopausal symptoms 1.

Hormone Replacement Therapy Consideration:

• For women with early or premature menopause without contraindications, HRT is recommended at least until the average age of natural menopause (approximately age 51) 1
• This patient underwent surgical menopause at age 47 and is now 50, making her an appropriate candidate 1
• HRT has favorable risk-benefit profile and can improve bone density, vasomotor symptoms, mood, and quality of life 1
• Requires discussion of individual risks and benefits 1

Fibromyalgia Consideration

If bone pathology and metabolic causes are excluded, consider fibromyalgia, which presents with:

• Chronic widespread pain
• Fatigue
• Sleep disturbance
• Anxiety/depression
• Absence of inflammatory markers or structural abnormalities

Management would include graded exercise programs, cognitive behavioral approaches, and potentially medications for neuropathic pain (gabapentin, pregabalin, or duloxetine) 1.

Critical Pitfalls to Avoid

• Do not attribute all symptoms to menopause or fibromyalgia without excluding serious bone pathology 1
• Do not delay DEXA scan - three years post-oophorectomy represents significant time for bone loss 1
• Do not miss Paget's disease - family history makes this a priority consideration requiring alkaline phosphatase and imaging 2, 3
• Do not overlook malignancy - diffuse pain in a 50-year-old requires systematic exclusion of metastatic disease 1
• Do not prescribe chronic NSAIDs or corticosteroids for non-inflammatory pain without definitive diagnosis 1

Immediate Action Plan

1. Order comprehensive metabolic bone panel (alkaline phosphatase, calcium, phosphate, vitamin D, PTH) 1, 2, 3
2. Order DEXA scan 1
3. Obtain plain radiographs of most symptomatic skeletal sites 1, 3
4. Check inflammatory markers and CBC 1
5. If alkaline phosphatase elevated: proceed with nuclear bone scan and targeted imaging 3, 4
6. If all bone pathology excluded: consider HRT for menopausal symptoms and structured exercise program for pain and fatigue 1