Osteoporosis Treatment
First-Line Therapy: Oral Bisphosphonates
For most patients with osteoporosis, initiate treatment with oral bisphosphonates—specifically alendronate 70 mg once weekly or risedronate 35 mg once weekly—as these agents have the strongest evidence for fracture reduction, are available as inexpensive generics, and should be continued for 5 years before reassessing. 1, 2
Specific Dosing Regimens
- Alendronate: 70 mg once weekly (or 10 mg daily for treatment; 35 mg weekly for prevention) 1, 2
- Risedronate: 35 mg once weekly (or 5 mg daily, or 150 mg once monthly) 1, 2, 3
- Zoledronic acid: 5 mg IV once yearly (alternative for patients unable to tolerate oral formulations) 2
Critical Administration Instructions
Oral bisphosphonates require strict adherence to administration guidelines to prevent esophageal complications and ensure absorption 3:
- Take immediately upon rising in the morning with at least 4 ounces of plain water 3
- Remain upright (standing or sitting) for at least 30 minutes after administration 3
- Take on an empty stomach; wait at least 30 minutes before consuming food, beverages, or other medications 1, 3
- Swallow tablets whole—never chew, cut, or crush 3
- For risedronate delayed-release formulation: Take immediately following breakfast (not fasting), as fasting increases risk of abdominal pain 3
When to Use Anabolic Agents First-Line
For patients at very high fracture risk, initiate treatment with anabolic agents (teriparatide or romosozumab) followed by mandatory transition to bisphosphonates or denosumab to maintain bone gains. 1, 4
Defining Very High Risk
Very high-risk patients include those with 4:
- Age >74 years
- Multiple prior osteoporotic fractures
- T-score ≤-3.0
- Recent vertebral or hip fracture
- FRAX scores ≥20% for major osteoporotic fracture or ≥3% for hip fracture
Teriparatide Protocol
- Dosing: 20 mcg subcutaneously daily for 18-24 months (maximum 2 years lifetime use) 2, 5
- Expected outcomes: 10% increase in spine BMD, 3% increase in hip BMD, 69 per 1000 reduction in vertebral fractures 4
- Mandatory sequential therapy: Must transition to bisphosphonate or denosumab immediately after completion to prevent rebound fractures 4, 2
- Contraindications to verify: Paget's disease, prior skeletal radiation, bone metastases, active malignancies prone to bone metastases 4
- Monitoring: Check serum calcium and urinary calcium at 1 month, then as clinically indicated 4
Romosozumab Considerations
- Conditionally recommended for very high-risk postmenopausal women, though evidence certainty is lower than for teriparatide 1, 4
- Must be followed by antiresorptive therapy 1
Second-Line Therapy: Denosumab
Reserve denosumab (60 mg subcutaneously every 6 months) for patients with contraindications to bisphosphonates or who experience adverse effects from bisphosphonates. 1, 2
Critical Safety Consideration
Never discontinue denosumab without immediately initiating sequential bisphosphonate therapy, as stopping causes severe rebound bone loss and multiple vertebral fractures. 2, 6 This represents one of the most dangerous pitfalls in osteoporosis management.
Denosumab-Specific Warnings
- Increased risk of serious infections (skin, abdomen, bladder, ear, endocarditis) 6
- Severe jaw bone problems (osteonecrosis) requiring dental examination before initiation 6
- Unusual thigh bone fractures with prolonged use 6
- Requires ongoing treatment indefinitely or planned transition to bisphosphonates 2, 6
Treatment Duration and Drug Holidays
Continue bisphosphonates for 5 years, then reassess fracture risk to determine if treatment interruption is appropriate. 1, 2
- Patients at low fracture risk after 5 years should be considered for drug discontinuation 2
- Patients at persistent high risk may benefit from continuation beyond 5 years, though this increases risk of rare complications (osteonecrosis of jaw, atypical femoral fractures) 1
- Do not monitor BMD during the initial 5-year treatment period, as it does not improve outcomes 2
- Reassess fracture risk periodically in patients who discontinue therapy 2
Essential Adjunctive Therapy for All Patients
Every patient with osteoporosis requires 1, 4, 2, 7:
Calcium and Vitamin D Supplementation
- Ages 51-70: 1,200 mg calcium, 600 IU vitamin D daily 1
- Ages 71+: 1,200 mg calcium, 800 IU vitamin D daily 1
- Target serum 25(OH)D level ≥20-30 ng/mL (some guidelines recommend ≥30-50 ng/mL) 1, 4
- Take calcium supplements at a different time of day than bisphosphonates to avoid absorption interference 1
Lifestyle Modifications
- Weight-bearing and muscle resistance exercises (squats, push-ups) 4, 7
- Balance exercises (heel raises, standing on one foot) 4, 7
- Fall prevention counseling 1, 4
- Smoking cessation 1, 4
- Alcohol reduction 1, 4
Special Populations
Men with Osteoporosis
Use the same bisphosphonate regimens as for postmenopausal women (alendronate, risedronate, or zoledronic acid), though evidence is weaker than for women. 2 Denosumab is second-line for men with contraindications to bisphosphonates 1.
Glucocorticoid-Induced Osteoporosis
For patients on ≥5 mg prednisone daily (or equivalent) for ≥6 months, initiate oral bisphosphonates for high-risk patients, or consider anabolic agents (teriparatide) for very high-risk patients. 2, 5
Renal Impairment
Do not prescribe bisphosphonates if creatinine clearance is <35 mL/min for zoledronic acid or <30 mL/min for oral bisphosphonates. 2 Consider alternative agents in these patients.
Critical Contraindications to Bisphosphonates
Bisphosphonates are contraindicated in patients with 3:
- Esophageal abnormalities that delay emptying (stricture, achalasia)
- Inability to stand or sit upright for at least 30 minutes
- Hypocalcemia (must correct before initiating therapy)
- Active upper GI problems (Barrett's esophagus, esophageal disease, active gastritis, duodenitis, ulcers)
Pitfalls to Avoid
Never use combination therapy (multiple osteoporosis drugs simultaneously), as it provides no additional fracture benefit 2
Never use hormone therapy or raloxifene as first-line treatment due to cardiovascular and thromboembolic risks, though raloxifene may be considered in younger postmenopausal women at lower fracture risk 1, 2
Never stop denosumab abruptly—always plan sequential bisphosphonate therapy to prevent catastrophic rebound vertebral fractures 2, 6
Never prescribe bisphosphonates without ensuring adequate calcium and vitamin D status, as bisphosphonates can worsen hypocalcemia 1, 3