What could be causing a month-long history of musculoskeletal ache with arm movement in an elderly female patient with hyperlipidemia, depression, and possible overactive bladder, taking Crestor (rosuvastatin), sertraline, vitamin D3, and a beta 3-adrenoceptor agonist?

Statin-Induced Myopathy is the Most Likely Cause

The month-long musculoskeletal ache with arm movement in this elderly female patient is most likely caused by statin-induced myopathy from Crestor (rosuvastatin), and you should immediately assess for muscle weakness, check creatine kinase levels, and consider temporarily discontinuing the statin while evaluating for other contributing factors. 1

Immediate Clinical Assessment Required

Before making any medication changes, perform the following evaluation:

• Assess for objective muscle weakness (not just pain) through physical examination of proximal muscle groups, particularly shoulders and upper arms 1
• Measure creatine kinase (CK) levels - if CK is >10 times upper limit of normal with evidence of renal injury, this represents rhabdomyolysis requiring immediate medical attention 1
• Check for predisposing factors that increase statin myopathy risk in this patient 1:
  • Female gender (present)
  • Advanced age (elderly, likely >65 years)
  • Small stature/low BMI
  • Concomitant medications using CYP450 pathway (sertraline uses this pathway)
  • Hypothyroidism
  • Renal or hepatic dysfunction

Why Rosuvastatin is the Primary Suspect

Statins cause a spectrum of muscle complaints that are more common among older adults, ranging from myalgias without CK elevation to fulminant rhabdomyolysis, and these complaints often include extremity weakness which can be debilitating for elderly patients. 1

• The FDA label for rosuvastatin specifically warns that muscle pain, tenderness, and weakness are more likely in patients who are 65 years of age or older 2
• Muscle problems may not resolve immediately even after statin discontinuation, requiring ongoing monitoring 2
• Elderly patients and their families may be less likely to articulate muscle complaints, assuming symptoms are related to arthritis or aging itself 1

Ruling Out Other Medication Causes

The beta-3 adrenoceptor agonist (likely mirabegron for overactive bladder) is unlikely to be the cause:

• Beta-3 agonists like mirabegron have a low occurrence of side effects, with the most common being hypertension, urinary tract infection, headache, and nasopharyngitis - not musculoskeletal pain 3
• Musculoskeletal adverse events are not characteristic of this drug class 4, 5

Sertraline (SSRI) is also an unlikely primary cause:

• While SSRIs can contribute to polypharmacy issues in elderly patients, musculoskeletal aches are not a typical adverse effect 1
• However, sertraline's metabolism through CYP450 may increase statin levels and compound myopathy risk 1

Recommended Management Algorithm

Step 1: If CK is normal or mildly elevated (<3x upper limit of normal):

• Temporarily discontinue rosuvastatin until symptoms improve (typically 2-4 weeks) 1
• Document baseline musculoskeletal symptoms for comparison 1
• Assess for reversible causes: hypothyroidism, vitamin D deficiency (though she's taking supplementation), electrolyte abnormalities 1

Step 2: After symptom resolution, implement rechallenge strategy:

• The majority of patients can be successfully treated with at least one statin using a modified approach 1
• Restart rosuvastatin at a lower dose (reduce from current dose by 50%) 1
• Consider alternative statin with different metabolism (e.g., pravastatin, which has less CYP450 interaction) 1
• Try alternative dosing regimen (every other day or twice weekly) 1

Step 3: Monitor for recurrent symptoms:

• If symptoms recur with rechallenge, this confirms statin-associated muscle symptoms (SAMS) 1
• In patients at increased ASCVD risk, the goal should be to treat with the maximally tolerated statin dose, even if lower than guideline-recommended 1

Critical Considerations for This Elderly Patient

Life expectancy and goals of care must guide statin continuation decisions:

• Clinical practice guidelines indicate a 1-year lag time until statin benefit is demonstrable for coronary heart disease 1
• Patients with conditions that severely compromise life expectancy or quality of life may not be suitable candidates for statins 1
• However, cardiovascular benefit from statins continues through about age 85, and secondary prevention guidelines advise lipid-lowering therapy "regardless of age" unless frailty, comorbidity, and polypharmacy confound management 1

Polypharmacy assessment is essential:

• This patient is on multiple medications, increasing risk for drug interactions and adverse effects 1
• Discontinuation of statins requires careful planning as it could be associated with adverse withdrawal effects 1
• Use tools like STOPP/START criteria or Beers criteria to identify potentially inappropriate medications 1

Common Pitfalls to Avoid

• Do not assume muscle aches are simply "normal aging" or arthritis - elderly patients often underreport statin-related symptoms 1
• Do not permanently discontinue statins without attempting rechallenge - most patients can tolerate an alternative regimen 1
• Do not ignore the possibility of statin-associated autoimmune myopathy (rare) - characterized by muscle weakness, marked and persistent CK elevation, presence of HMGCR antibodies, and lack of resolution on statin discontinuation; this requires statin cessation and immunosuppressive therapy 1
• Do not check CK levels routinely in asymptomatic patients - only measure when symptoms are present 1

Alternative Diagnosis Considerations

If symptoms persist after statin discontinuation, consider:

• Polymyalgia rheumatica (bilateral shoulder and hip girdle pain in elderly patients)
• Rotator cuff pathology (though bilateral arm involvement is less typical)
• Cervical radiculopathy
• Inflammatory arthritis
• Hypothyroidism (check TSH)
• Vitamin D deficiency (though supplementing, check 25-OH vitamin D level)