What are the guidelines for treating osteoporosis?

Osteoporosis Treatment Guidelines

First-Line Treatment: Oral Bisphosphonates

Oral bisphosphonates (alendronate or risedronate) are the recommended first-line pharmacologic treatment for both postmenopausal women and men with osteoporosis at high risk for fracture. 1, 2, 3

• These agents have strong evidence for reducing vertebral fractures (risk difference -52 per 1000 person-years), hip fractures (risk difference -6 per 1000 person-years), and non-vertebral fractures 1, 4
• Generic formulations should be prescribed whenever possible due to significantly lower cost with equivalent efficacy 1, 3
• Alendronate 70 mg once weekly or risedronate are therapeutically equivalent to daily dosing and improve adherence 1, 5

Treatment Duration and Drug Holidays

• Treat with bisphosphonates for 5 years initially, then reassess fracture risk to determine whether to continue or take a drug holiday 1, 2, 3
• After 5 years of oral bisphosphonate therapy, if moderate-to-high fracture risk persists, continue treatment for 7-10 years total, switch to IV bisphosphonate if absorption/adherence is problematic, or consider another drug class 1
• Patients at lower risk after 5 years can discontinue treatment temporarily 2, 3

Second-Line Treatment: Denosumab

Denosumab 60 mg subcutaneously every 6 months is recommended as second-line therapy for patients with contraindications to or intolerance of bisphosphonates. 1, 2, 3

Critical Warning About Denosumab Discontinuation

• Denosumab discontinuation causes rebound bone loss and multiple vertebral fractures; patients MUST transition to bisphosphonate therapy after stopping denosumab 1, 2, 3, 6
• This is not optional—sequential therapy with an antiresorptive agent is mandatory to prevent catastrophic rebound fractures 1, 2
• Do not stop, skip, or delay denosumab doses without planning sequential therapy 6

Very High-Risk Patients: Anabolic Agents First

For patients at very high risk for fracture, initiate anabolic agents (teriparatide, abaloparatide, or romosozumab) BEFORE bisphosphonates, followed by mandatory transition to antiresorptive therapy. 1, 2, 3

Defining Very High Risk

Very high risk includes patients with: 3

• Age >74 years
• Recent fracture within 12 months
• Multiple prior osteoporotic fractures
• T-score ≤-3.0
• Fractures despite ongoing bisphosphonate therapy
• 10-year FRAX risk of major osteoporotic fracture ≥20% or hip fracture ≥3%

Specific Anabolic Agent Recommendations

• Teriparatide reduces vertebral fractures by 69 per 1000 patients and clinical fractures by 27 per 1000 patients 3
• Abaloparatide is supported by the strongest BMD data for men with osteoporosis at very high risk 1
• Romosozumab is conditionally recommended for very high-risk postmenopausal women, limited to 12 monthly doses due to waning anabolic effect 3
• Anabolic agents should be limited to 2 years maximum, then MUST be followed by antiresorptive therapy to maintain bone gains 2, 3, 7

Sequential Therapy is Mandatory

• Patients initially treated with anabolic agents must be offered an antiresorptive agent after discontinuation to preserve gains and prevent serious risk of rebound and multiple vertebral fractures 1, 2
• This applies to all anabolic agents: teriparatide, abaloparatide, and romosozumab 1, 2

Glucocorticoid-Induced Osteoporosis

For patients on ≥2.5 mg/day of glucocorticoids for >3 months, perform fracture risk assessment within 6 months of starting therapy. 1, 2

• Screening should include FRAX score (for patients ≥40 years), BMD with vertebral fracture assessment (VFA) or spine x-rays 1, 2
• Oral bisphosphonates are strongly recommended for patients at high or very high fracture risk 1, 2
• For very high fracture risk, anabolic agents (teriparatide or PTH-related protein) are conditionally recommended over antiresorptive agents 1
• Prevention is recommended when prednisone dose is >7.5 mg daily 1

Essential Adjunctive Measures for ALL Patients

All patients with osteoporosis require the following non-pharmacologic interventions: 1, 2, 3, 4

• Calcium 1000-1200 mg daily
• Vitamin D 800-1000 IU daily (target serum level ≥20 ng/mL)
• Weight-bearing and muscle resistance exercises (squats, push-ups)
• Balance exercises (heel raises, standing on one foot) and fall prevention counseling
• Smoking cessation
• Alcohol reduction (avoid excessive intake)

Screening and Diagnosis

DEXA scanning should be performed in: 3

• All women aged ≥65 years
• Postmenopausal women <65 years with risk factors
• Men aged ≥65 years 1
• Men <65 years with risk factors

Treatment Thresholds

Treatment is indicated for: 3

• T-score ≤-2.5
• T-score between -1.0 and -2.5 with 10-year FRAX risk of major osteoporotic fracture ≥20% or hip fracture ≥3%
• Low-trauma fracture, even if DEXA does not indicate osteoporosis

All patients with a prior fragility fracture should be strongly considered for treatment with anti-osteoporosis medications. 1

Monitoring

• BMD testing should be performed every 1-2 years until stable, then every 2-3 years 2
• Bone density monitoring should not be performed during the initial 5-year pharmacologic treatment period 3
• Biochemical markers of bone turnover are appropriate tools to assess adherence to anti-resorptive therapy 1
• Assess for medication side effects at each visit, including rare complications like osteonecrosis of the jaw and atypical femoral fractures 2, 7, 6

Special Considerations for Men

The same treatment algorithm applies to men as to postmenopausal women, with oral bisphosphonates as first-line and denosumab as second-line therapy. 1

• Serum total testosterone should be assessed as part of pre-treatment evaluation 1
• Appropriate hormone replacement therapy should be considered in men with low levels of total or free serum testosterone 1

Critical Safety Warnings

Bisphosphonates

• Monitor for rare adverse effects including osteonecrosis of the jaw and atypical femoral fractures, which may increase with duration of therapy 1, 2
• Must be taken in fasting state with water at least 30 minutes before consuming food or beverages 5

Teriparatide

• In animal studies, teriparatide caused osteosarcoma in rats; however, no increased risk has been observed in adult humans 7
• May cause transient hypercalcemia and orthostatic hypotension 7
• Should not be used in children and young adults whose bones are still growing 7

Denosumab

• Severe jaw bone problems (osteonecrosis) may occur 6
• Increased risk of serious infections, including skin, abdominal, bladder, ear, and endocarditis 6
• Unusual thigh bone fractures can occur 6
• Most critical: rebound vertebral fractures after discontinuation if not followed by antiresorptive therapy 6

Fracture Liaison Services

Comprehensive inpatient or outpatient fracture liaison services increase medication initiation and adherence by 38% compared with 17% for patients without these services (risk difference 20%), which may reduce subsequent fracture rates. 4