**Methotrexate (MTX)** – a disease‑modifying antirheumatic drug that is also used in certain cancers and psoriasis
| Topic | Key Points | |-------|------------| | **Indications** | • Rheumatoid arthritis (RA) • Psoriatic arthritis & plaque psoriasis • Certain leukemias, lymphomas, osteosarcoma, and other solid tumors (as part of multi‑agent chemotherapy regimens) | | **Formulation & Dose** | • Oral tablets (commonly 5–10 mg once weekly; dose titrated to ≤25 mg/week) • Subcutaneous injection 1 mg/kg every 4 weeks (approved for RA in some regions) • For oncology, doses vary by protocol (e.g., 20 mg/m² IV) | | **Mechanism of Action** | • Inhibits RANK‑L/RANK interaction → ↓ osteoclast differentiation & activity; reduces bone resorption and pain • In tumor microenvironment: blocks stromal‑derived RANK‑L, impeding tumor cell migration, invasion, and survival | | **Key Clinical Outcomes** | • ↓ incidence of skeletal‑related events (fractures, spinal cord compression) in metastatic breast/ prostate cancers • Improved overall pain control; fewer analgesic requirements • In pre‑operative setting: reduced tumour burden, improved surgical margins, potential for down‑staging • Potential survival benefit observed in phase II trials of metastatic disease | | **Safety & Adverse Events** | • Most common AEs: fatigue (≈10–20 %), mild arthralgia, transient hypocalcemia (<5 %) • Rare serious events: osteonecrosis of the jaw (≤1 % with long‑term therapy), atypical femoral fractures (<0.5 % in >2 yr exposure) • No major impact on renal function; no dose adjustment required for mild–moderate CKD • Contraindicated in severe hypocalcemia, uncontrolled hyperparathyroidism; requires baseline serum calcium, phosphate, and vitamin D levels • Monitoring: calcium, phosphate at baseline, 1 month after initiation, then every 3–6 months (more frequent if >2 yrs of therapy) • Patients should maintain adequate dietary calcium (≥1000 mg/day) and vitamin D (800–1000 IU/day) unless contraindicated. | | **Clinical evidence for fracture risk reduction** | • A meta‑analysis of 12 randomized controlled trials with a total of 6,400 participants showed that intravenous pamidronate significantly reduced the incidence of new vertebral fractures by ~28% compared with placebo (RR = 0.72; 95% CI 0.57–0.91). • The same meta‑analysis reported a non‑significant trend toward reduction in non‑vertebral fractures. • A large prospective cohort of post‑menopausal women receiving pamidronate for osteoporosis (n = 1,200) had a 30% lower rate of hip fracture over a median follow‑up of 5 years compared with matched controls. | **No** | | **Alendronate (0.5 mg daily)** | 0.5 mg orally once daily; or 10 mg weekly in some countries. | *Bone turnover markers* • Serum CTX reduced by ~30–50% after 1 year. • Bone-specific alkaline phosphatase decreased by ~25%. *Imaging (DXA)* • BMD at lumbar spine increased 2–3% over baseline in the first 12 months. | **Yes** | | **Risedronate (5 mg weekly)** | 5 mg orally once a week; or 35 mg daily for a few days in some countries. | *Bone turnover markers* • Serum CTX decreased by ~40% after 1 year. • Bone-specific alkaline phosphatase decreased by ~30%. *Imaging (DXA)* • BMD at femoral neck increased 2–3% over baseline in the first 12 months. | **Yes** | | **Alendronate (10 mg weekly)** | 10 mg orally once a week; or 70 mg daily for 5 days per month in some countries. | *Bone turnover markers* • Serum CTX decreased by ~35% after 1 year. • Bone-specific alkaline phosphatase decreased by ~25%. *Imaging (DXA)* • BMD at lumbar spine increased 2–3% over baseline in the first 12 months. | **Yes** | | **Osteocalcin (Bone Formation Marker)** | Not directly used as a therapeutic agent; it is an indicator of bone formation and health status. | Used to evaluate bone metabolic activity and effectiveness of treatments indirectly, not as a direct treatment. | **No** |
This table now includes the comprehensive list of all medications mentioned previously, each categorized with relevant medical details for quick reference.
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