6.9 Musculoskeletal and Rheumatologic Pharmacotherapy
Key Takeaways
- Acetaminophen up to 4 g daily in healthy adults, reduced to about 2 g in hepatic impairment or chronic alcohol use, remains the first-line systemic analgesic for osteoarthritis; topical NSAIDs are preferred for knee and hand disease.
- Rheumatoid arthritis requires a disease-modifying antirheumatic drug within three months of diagnosis, with methotrexate as the anchor and folic acid supplementation mandatory.
- Allopurinol is started low and titrated to a serum urate target below 360 micromol/L, or below 300 micromol/L with tophi, and is continued through an acute gout flare once established.
- Bisphosphonates must be taken on an empty stomach with a full glass of plain water while remaining upright for at least 30 minutes to prevent esophageal injury.
- HLA-B*5801 screening before allopurinol is recommended in patients of Han Chinese, Thai, or Korean ancestry because of severe cutaneous adverse reaction risk.
6.9 Musculoskeletal and Rheumatologic Pharmacotherapy
Exam Focus: These conditions generate high-yield items because the drugs carry demanding monitoring requirements and precise administration rules. Expect questions on treat-to-target urate lowering, methotrexate safety, and bisphosphonate administration.
Osteoarthritis
Osteoarthritis is degenerative joint disease with cartilage loss, subchondral bone change, and osteophyte formation. Pain is activity-related, morning stiffness lasts under 30 minutes, and there is little systemic inflammation — the mirror image of rheumatoid arthritis.
Non-pharmacological therapy carries the strongest evidence: structured exercise, weight loss where relevant, and physiotherapy.
Drug therapy escalates:
- Topical NSAIDs (diclofenac gel) for knee and hand osteoarthritis, preferred in older adults because systemic exposure is a fraction of oral therapy.
- Acetaminophen, modest but safe; maximum 4 g daily in healthy adults, reduced to about 2 g with hepatic impairment, chronic alcohol use, low body weight, or malnutrition. Screen every non-prescription combination product for hidden acetaminophen.
- Oral NSAIDs at the lowest effective dose for the shortest time, with gastroprotection when risk factors are present (age over 65, prior ulcer, concurrent anticoagulant, corticosteroid, or antiplatelet).
- Intra-articular corticosteroid for a flare, or duloxetine for chronic pain with a central component.
Opioids offer little benefit in osteoarthritis and carry substantial harm; glucosamine and chondroitin have not shown consistent benefit over placebo.
Rheumatoid Arthritis
Rheumatoid arthritis is a symmetric, inflammatory polyarthritis of the small joints with morning stiffness lasting more than an hour, systemic symptoms, and radiographic erosion if untreated.
The core principle is the window of opportunity: start a conventional synthetic disease-modifying antirheumatic drug (DMARD) within three months of diagnosis to prevent irreversible joint destruction. Corticosteroids and NSAIDs relieve symptoms but do not modify disease.
| Drug | Key monitoring | Counselling essentials |
|---|---|---|
| Methotrexate | Complete blood count, liver enzymes, creatinine every 2 to 4 weeks initially, then every 12 weeks | Weekly dosing; folic acid 1 to 5 mg daily on non-methotrexate days; avoid in pregnancy and stop 3 months before conception; limit alcohol |
| Hydroxychloroquine | Baseline and periodic ophthalmologic examination | Retinal toxicity is dose- and duration-related |
| Sulfasalazine | Complete blood count, liver enzymes | Orange discolouration of urine; caution in sulfonamide allergy and G6PD deficiency |
| Leflunomide | Liver enzymes, blood pressure | Very long half-life; cholestyramine washout needed before pregnancy |
| Biologic DMARDs | Screen for latent tuberculosis and hepatitis B before starting | Hold during serious infection; live vaccines contraindicated |
The most catastrophic and most examined methotrexate error is daily rather than weekly administration, which causes fatal pancytopenia and mucositis. Confirm the day of the week at every dispense.
Gout and Hyperuricemia
An acute flare is monoarticular, intensely painful, and often affects the first metatarsophalangeal joint. Treat the flare with an NSAID, colchicine, or corticosteroid; the choice depends on comorbidity, not on superiority.
- Colchicine dosing for a flare is 1.2 mg followed by 0.6 mg one hour later. Higher historical regimens caused severe diarrhea without added benefit. Reduce the dose in renal impairment and with strong CYP3A4 or P-glycoprotein inhibitors such as clarithromycin, which can precipitate fatal toxicity.
- Urate-lowering therapy is indicated for recurrent flares, tophi, urate nephrolithiasis, or radiographic damage. Allopurinol is first-line, started at 100 mg daily (50 mg in chronic kidney disease) and titrated every 2 to 5 weeks to a serum urate below 360 micromol/L, or below 300 micromol/L with tophaceous disease.
- Never stop established urate-lowering therapy during an acute flare; fluctuating urate prolongs the attack. When starting therapy, provide flare prophylaxis with low-dose colchicine or an NSAID for three to six months.
- HLA-B*5801 testing before allopurinol is recommended in patients of Han Chinese, Thai, or Korean ancestry because of the risk of severe cutaneous adverse reactions.
Review drugs that raise urate: thiazide and loop diuretics, low-dose acetylsalicylic acid, and calcineurin inhibitors. Losartan and SGLT2 inhibitors modestly lower urate and may be useful in a patient who needs both indications treated.
Osteoporosis
Fracture risk, not bone mineral density alone, drives treatment. Canadian practice uses a risk assessment tool combining age, sex, femoral neck bone mineral density, prior fragility fracture, glucocorticoid use, and parental hip fracture.
Universal measures: 1,000 to 1,200 mg of elemental calcium daily from diet plus supplement if needed, 800 to 2,000 IU of vitamin D daily, weight-bearing and resistance exercise, smoking cessation, alcohol moderation, and falls-risk review.
| Class | Examples | Key points |
|---|---|---|
| Bisphosphonates | Alendronate, risedronate, zoledronic acid | First-line; oral products require strict administration technique |
| RANK ligand inhibitor | Denosumab | Subcutaneous every 6 months; missed doses cause rapid bone loss and rebound vertebral fractures, so continuity is critical |
| Anabolic | Teriparatide, romosozumab | Reserved for severe or very high risk disease |
| Selective estrogen receptor modulator | Raloxifene | Reduces vertebral fracture; increases venous thromboembolism risk |
Oral bisphosphonate administration is a classic examination item: take first thing in the morning on an empty stomach with a full glass of plain water, remain upright and take nothing else by mouth for at least 30 minutes (60 minutes for ibandronate). Mineral water, coffee, calcium, iron, and antacids all block absorption. Failure to remain upright causes erosive esophagitis.
Long-term bisphosphonate use is associated with osteonecrosis of the jaw and atypical femoral fracture; encourage a dental examination before starting and consider a drug holiday after 3 to 5 years in patients whose risk has fallen.
Soft Tissue Injury and Acute Low Back Pain
For strains, sprains, and tendinitis, relative rest with early mobilisation, ice, compression, and elevation are combined with topical or oral NSAIDs. For acute non-specific low back pain, advise staying active, reassure that most episodes resolve within six weeks, and use NSAIDs first-line. Refer urgently for red flags: bowel or bladder dysfunction, saddle anesthesia, progressive neurological deficit, fever with intravenous drug use, or a history of malignancy.
A patient with tophaceous gout is on allopurinol 300 mg daily with a serum urate of 395 micromol/L. He presents with an acute flare of the right great toe. What should happen to the allopurinol?
Which instruction is essential when dispensing oral alendronate?
A patient newly diagnosed with rheumatoid arthritis is prescribed methotrexate. Which supportive therapy should be initiated at the same time?
An 80-year-old with knee osteoarthritis, chronic kidney disease stage G3b, and a prior gastrointestinal bleed asks for pain relief. Which is the most appropriate initial recommendation?