An elderly woman with grade‑2 knee osteoarthritis who has been taking alendronate (Altraday) once daily for four years now presents with worsening knee pain, neuropathic‑type pain radiating to the ankle, and mild‑to‑moderate swelling of the lower leg and foot; what is the appropriate management?

Management of Worsening Knee Pain with Neuropathic Features and Limb Swelling in an Elderly Woman on Long-term Alendronate

Stop the alendronate immediately and reassess the entire clinical picture, as this patient requires urgent evaluation for the unilateral limb swelling (to rule out deep vein thrombosis or other vascular pathology) before addressing the osteoarthritis pain, and the alendronate should be discontinued after 4 years of therapy based on evidence that fracture protection persists for up to 5 years after stopping bisphosphonates. 1

Immediate Priority: Evaluate the Unilateral Limb Swelling

• Urgent vascular assessment is mandatory – unilateral leg swelling with pain from knee to toes raises concern for deep vein thrombosis, compartment syndrome, or other serious vascular/lymphatic pathology that requires immediate diagnostic workup before any osteoarthritis treatment modifications. 1
• The neuropathic pain radiating below the knee to ankle combined with swelling suggests this may not be purely osteoarthritis progression and warrants neurological and vascular evaluation. 1

Discontinue Alendronate After 4 Years of Therapy

• The FLEX trial demonstrates that patients taking alendronate for longer than 5 years can stop therapy and still maintain fracture protection for up to 5 more years, making continuation unnecessary after 4 years, especially given the patient's clinical context. 1
• Continuing bisphosphonates beyond 4-5 years increases risks of atypical fractures and osteonecrosis without additional benefit in most patients. 1
• Check vitamin D blood levels and ensure adequate calcium (1,200 mg/day) and vitamin D (1,000 IU/day) intake through diet and supplementation taken once daily to improve adherence. 1

Address the Worsening Knee Osteoarthritis Pain

First-Line Pharmacologic Management

• Start acetaminophen (paracetamol) at regular doses of 3,000 mg daily (not exceeding 3,000 mg in elderly patients to minimize hepatotoxicity risk), taken in divided doses throughout the day rather than "as needed" for better sustained pain control. 1, 2
• Acetaminophen is the safest first-line option with comparable efficacy to NSAIDs in many elderly patients with osteoarthritis, and should be tried before escalating to other agents. 1, 2

Second-Line: Topical Agents Before Oral NSAIDs

• Apply topical diclofenac gel to the affected knee twice daily if acetaminophen provides insufficient relief, as topical NSAIDs have minimal systemic absorption and avoid the gastrointestinal, renal, and cardiovascular risks of oral NSAIDs. 1, 2, 3
• Topical capsaicin cream (0.025-0.075%) applied 3-4 times daily is an alternative non-NSAID topical option, though it requires 2-4 weeks of continuous use before therapeutic effect and causes initial burning in 35-100% of patients. 4

Third-Line: Consider Duloxetine for Neuropathic Component

• Duloxetine 30 mg once daily for 1 week, then increase to 60 mg once daily is conditionally recommended for knee osteoarthritis and may be particularly appropriate given the neuropathic-type pain radiating to the ankle. 1, 5
• Duloxetine addresses both osteoarthritis pain and neuropathic pain components, with evidence supporting efficacy when used alone or combined with other analgesics. 1, 5
• Maximum dose is 60 mg daily for osteoarthritis; higher doses provide no additional benefit and increase adverse effects. 1, 5

Fourth-Line: Intra-articular Corticosteroid Injection

• Intra-articular corticosteroid injection into the affected knee provides effective short-term pain relief, particularly for acute flares with effusion, and is strongly recommended for elderly patients who cannot tolerate oral NSAIDs. 1, 2
• This intervention is appropriate if the swelling is confirmed to be joint effusion rather than systemic edema. 1, 2

Oral NSAIDs Only as Last Resort

• Oral NSAIDs should only be considered after topical agents have failed, and only at the lowest effective dose for the shortest duration, with mandatory co-prescription of a proton pump inhibitor for gastroprotection. 1, 2
• Elderly patients face substantially higher risks of gastrointestinal bleeding, renal insufficiency, and cardiovascular complications with oral NSAIDs, making them inappropriate as initial therapy. 1, 2
• Assess renal function before prescribing any oral NSAID, as they are contraindicated or require extreme caution in renal insufficiency. 1, 2

Essential Non-Pharmacologic Core Treatments

• Joint-specific strengthening exercises and general aerobic conditioning must accompany any pharmacologic management, with effect sizes of 0.57-1.0 for pain reduction in multiple randomized trials. 1, 2
• Both supervised and home-based exercise programs demonstrate reduced pain scores and improved function. 2
• Weight reduction if overweight or obese significantly decreases knee osteoarthritis symptoms and progression. 2
• Patient education, local heat or cold applications, and assistive devices (walker, cane) with shock-absorbing footwear are essential complementary interventions. 1, 2

Critical Pitfalls to Avoid

• Never ignore unilateral limb swelling – this requires urgent evaluation before attributing all symptoms to osteoarthritis progression. 1
• Never continue bisphosphonates indefinitely – after 4-5 years, fracture protection persists without ongoing therapy, and continuation increases risks. 1
• Never prescribe oral NSAIDs without gastroprotection (proton pump inhibitor co-prescription) in any patient, especially the elderly. 1, 2
• Never exceed 3,000 mg daily of acetaminophen in elderly patients to prevent hepatotoxicity. 2
• Do not prescribe glucosamine or chondroitin – current evidence does not support their efficacy for osteoarthritis. 1, 2, 4
• Avoid tramadol and other opioids except as absolute last resort when all other options have been exhausted, due to high risk of toxicity, dependence, and minimal long-term benefit. 1