Osteoporosis drugs either slow bone breakdown (antiresorptives) or build new bone (anabolics).

• Bisphosphonates (alendronate, risedronate, ibandronate, zoledronic acid) bind bone mineral and are taken up by osteoclasts, which then stop resorbing bone. They stay in bone for years
• Denosumab is a monoclonal antibody against RANKL, the signal that forms and activates osteoclasts. Its effect wears off within months of a missed dose
• Raloxifene (selective estrogen receptor modulator, SERM) acts like estrogen on bone but blocks estrogen in breast and uterus
• Teriparatide and abaloparatide (parathyroid hormone analogs, given intermittently) stimulate osteoblasts
• Romosozumab blocks sclerostin → builds bone and reduces resorption
• Calcium and vitamin D supply raw material; they are required with every osteoporosis drug

Gout drugs

• Acute flare: NSAIDs and corticosteroids reduce inflammation; colchicine blocks microtubule formation in neutrophils, stopping their migration into the joint. None of these lowers urate
• Urate-lowering therapy (ULT): xanthine oxidase inhibitors (allopurinol, febuxostat) reduce urate production; probenecid (uricosuric) increases renal urate excretion; pegloticase (recombinant uricase) converts urate to soluble allantoin

Rheumatoid arthritis (RA) drugs

• Conventional synthetic DMARDs: methotrexate (folate antagonist with anti-inflammatory effects at low weekly doses), hydroxychloroquine, sulfasalazine, leflunomide (blocks pyrimidine synthesis in lymphocytes)
• Biologic DMARDs: TNF inhibitors (adalimumab, etanercept, infliximab, certolizumab, golimumab), abatacept (T-cell costimulation blocker), rituximab (B-cell depletion), tocilizumab and sarilumab (IL-6 receptor blockers)
• Targeted synthetic DMARDs: JAK inhibitors (tofacitinib, baricitinib, upadacitinib) block intracellular cytokine signaling
• Glucocorticoids and NSAIDs control symptoms as a bridge but do not stop joint destruction; DMARDs do

Bisphosphonates: esophagitis and esophageal ulcer (oral), musculoskeletal pain, acute-phase reaction (fever, myalgia) after IV doses, hypocalcemia; rare osteonecrosis of the jaw (ONJ) and atypical femur fracture (new thigh or groin pain).

Denosumab: hypocalcemia (boxed warning for severe hypocalcemia in advanced chronic kidney disease, especially dialysis), skin infection and dermatitis, ONJ, atypical femur fracture; rebound bone loss and multiple vertebral fractures if doses are delayed or stopped.

Raloxifene: hot flashes, leg cramps; boxed warning: VTE and death from stroke in women with or at risk of coronary disease.

Teriparatide/abaloparatide: orthostatic hypotension (first doses sitting or lying), hypercalcemia, nausea, leg cramps.

Romosozumab: boxed warning: MI, stroke, cardiovascular death; ONJ; hypocalcemia.

Colchicine: diarrhea, nausea, vomiting, abdominal pain; with toxicity — bone marrow suppression, myopathy, neuropathy, multiorgan failure.

Allopurinol: rash; rarely severe cutaneous reactions (Stevens–Johnson syndrome/toxic epidermal necrolysis, DRESS) — higher risk with HLA-B*58:01, CKD, and high starting doses; flares during the first months of ULT; liver enzyme elevation.

Febuxostat: liver enzyme elevation, flares, cardiovascular death (boxed warning).

Probenecid: uric acid kidney stones, GI upset, rash.

Methotrexate (boxed warnings: embryo-fetal toxicity; serious toxic reactions including death): mouth ulcers, nausea, hepatotoxicity, bone marrow suppression, pneumonitis (dry cough, dyspnea), infection, hair thinning; teratogenic.

Hydroxychloroquine: retinal toxicity (dose-related, after years of use), QT prolongation, GI upset, hypoglycemia, skin pigmentation.

Sulfasalazine: GI upset, rash, orange-yellow urine and skin, hemolysis in G6PD deficiency, reversible low sperm count, cytopenias.

Leflunomide: diarrhea, hepatotoxicity, hypertension, teratogenic (persists up to 2 years — cholestyramine washout before a planned pregnancy).

Biologics: injection-site or infusion reactions, serious infections, reactivation of TB and hepatitis B, demyelination and heart-failure worsening (TNF inhibitors), lymphoma and skin cancer risk; rituximab boxed warnings — fatal infusion reactions, severe mucocutaneous reactions, hepatitis B reactivation, progressive multifocal leukoencephalopathy (PML).

JAK inhibitors: serious infections, herpes zoster, thrombosis, major adverse cardiovascular events, malignancy, lipid elevation.

Oral bisphosphonates: contraindicated with esophageal disorders (stricture, achalasia), inability to sit or stand upright for 30 minutes, hypocalcemia, and severe kidney impairment (creatinine clearance below 30–35 mL/min). Zoledronic acid: creatinine clearance below 35 mL/min and hypocalcemia. Dental work: complete invasive dental treatment before starting when possible.

Denosumab: hypocalcemia must be corrected first; not for use in pregnancy.

Raloxifene: history of VTE, pregnancy, prolonged immobilization (stop at least 72 hours before).

Romosozumab: MI or stroke in the past year.

Colchicine: strong CYP3A4 or P-glycoprotein inhibitors (clarithromycin, ketoconazole, ritonavir, cyclosporine, verapamil, diltiazem) → fatal toxicity; reduce dose or avoid in severe kidney or liver disease; statins add myopathy risk.

Allopurinol: azathioprine and mercaptopurine (xanthine oxidase metabolizes them → severe marrow suppression; dose reduction required); ampicillin/amoxicillin increases rash; warfarin effect may rise. Febuxostat is contraindicated with azathioprine and mercaptopurine.

Probenecid: ineffective with low kidney function; history of uric acid stones; salicylates block its effect; it raises levels of penicillins and methotrexate.

Pegloticase: G6PD deficiency (hemolysis, methemoglobinemia); stop oral ULT during therapy (masks loss of response).

Methotrexate: pregnancy (contraindicated) and breastfeeding, significant liver disease or alcohol use disorder, kidney impairment, active infection, blood dyscrasias. Trimethoprim-sulfamethoxazole and other folate antagonists → severe marrow suppression; NSAIDs, PPIs, and probenecid can raise levels (mainly at high oncology doses). Stop methotrexate about 1–3 months before planned conception.

Biologics and JAK inhibitors: active serious infection, untreated latent TB; no live vaccines during therapy; TNF inhibitors are avoided in moderate–severe heart failure and demyelinating disease. Many biologics can be continued in pregnancy per specialist guidance.

NSAIDs: avoid from 20 weeks of pregnancy (FDA 2020); GI bleeding, kidney injury, cardiovascular risk.

1. Osteoporosis therapy
   • Check calcium and vitamin D before starting any antiresorptive; check calcium before each denosumab dose; creatinine before zoledronic acid
   • Dental assessment before starting; ask about jaw pain, loose teeth
   • Keep denosumab on schedule (every 6 months); flag any delay
   • Bone density follow-up; reassess bisphosphonate "drug holiday" after 3–5 years
2. Gout therapy
   • Serum urate every 2–5 weeks while titrating ULT, then every 6 months; target below 6 mg/dL (360 µmol/L)
   • HLA-B*58:01 testing before allopurinol in people of Southeast Asian descent (e.g., Han Chinese, Korean, Thai) and African American people
   • Flare prophylaxis (low-dose colchicine, NSAID, or prednisone) for at least 3–6 months when starting ULT
   • Kidney and liver function; CBC with colchicine long-term; encourage fluids with probenecid (unless restricted)
   • Do not stop established ULT during a flare
3. RA therapy
   • Methotrexate: verify weekly dosing on every order (daily dosing errors have caused deaths); give folic acid; CBC, liver enzymes, and creatinine at baseline, every 2–4 weeks for the first 3 months, then every 8–12 weeks; baseline chest X-ray and hepatitis B/C screening; pregnancy test
   • Before biologics/JAK inhibitors: latent TB test (IGRA or skin test), hepatitis B screening, update non-live vaccines; hold the dose and report fever or infection
   • Hydroxychloroquine: baseline eye exam, then yearly screening after 5 years (sooner with risk factors); dose not above 5 mg/kg actual body weight per day
   • JAK inhibitors: lipids, CBC, liver enzymes

• Alendronate: on waking, whole tablet with 180–240 mL of plain water, stay upright at least 30 minutes (60 minutes for ibandronate) and take nothing else by mouth until then; never with coffee, juice, milk, calcium, or antacids; report heartburn, painful swallowing, or chest pain
• Calcium 1,000–1,200 mg/day from diet plus supplements and vitamin D as advised; separate calcium from bisphosphonates, levothyroxine, iron, and some antibiotics
• Weight-bearing exercise, fall prevention, no smoking, limit alcohol
• Denosumab: keep every appointment; report muscle cramps, tingling around the mouth, or twitching
• Gout: take ULT every day, even without symptoms; early flares do not mean the drug is failing; stop allopurinol and seek care at the first sign of rash; limit alcohol, organ meats, and sugar-sweetened drinks
• Colchicine: stop and call if diarrhea, vomiting, or muscle weakness develops; avoid grapefruit juice and check every new drug with the pharmacist
• Methotrexate: take one day a week only; take folic acid; avoid alcohol; use reliable contraception; report mouth sores, fever, bruising, cough, or shortness of breath
• Biologics/JAK inhibitors: report fever or infection early; no live vaccines; teach subcutaneous injection technique and sharps disposal
• Sulfasalazine may turn urine and skin orange-yellow and stain contact lenses

• Alendronate: empty stomach, full glass of plain water, upright 30 minutes
• Denosumab: check calcium before each dose; never stop without a follow-up drug
• Raloxifene → VTE; romosozumab → cardiovascular boxed warning; teriparatide → orthostatic hypotension
• Acute gout: NSAID, colchicine, or steroid — they do not lower urate
• Allopurinol: start low, treat to urate below 6 mg/dL, prophylaxis for 3–6 months, stop at first rash
• HLA-B*58:01 testing in higher-risk Asian and African American clients
• Allopurinol + azathioprine/mercaptopurine → severe marrow suppression
• Colchicine + clarithromycin (CYP3A4/P-gp inhibitors) → fatal toxicity
• Methotrexate: weekly, folic acid, teratogenic, CBC/liver/creatinine; toxicity → leucovorin
• Screen TB and hepatitis B before biologics and JAK inhibitors; no live vaccines
• Hydroxychloroquine → eye exams