What should be advised to a postmenopausal woman or a man at high risk of fracture with osteoporosis prior to initiation of teriparatide (parathyroid hormone-related protein) monotherapy?

Pre-Treatment Counseling for Teriparatide (Monjaro) in Osteoporosis

Before initiating teriparatide, patients must understand that this medication requires mandatory transition to bisphosphonate or denosumab therapy after completion to prevent rapid bone loss and rebound vertebral fractures, is limited to a maximum 24-month lifetime treatment duration, and must be administered as daily subcutaneous self-injections. 1, 2, 3

Critical Safety Warnings and Contraindications

Osteosarcoma Risk and Absolute Contraindications

• Avoid teriparatide in patients with increased osteosarcoma risk, including those with open epiphyses, metabolic bone diseases (especially Paget's disease), bone metastases or history of skeletal malignancies, prior external beam or implant radiation therapy involving the skeleton, and hereditary disorders predisposing to osteosarcoma 4
• The medication is contraindicated in pediatric patients due to increased baseline osteosarcoma risk in patients with open epiphyses 3, 4
• Do not use in patients with history of malignancy prone to metastasize to bone, including those with potential micrometastatic or occult disease 1

Cardiovascular Considerations

• Unlike romosozumab (which increases cardiovascular events with HR 1.9), teriparatide does not carry cardiovascular contraindications and is the preferred anabolic agent for patients with recent myocardial infarction or stroke 1

Metabolic and Renal Concerns

• Avoid in patients with underlying hypercalcemic disorders (e.g., hyperparathyroidism) as teriparatide causes hypercalcemia more frequently than other osteoporosis agents 3, 4
• Consider risk/benefit carefully in patients with active or recent urolithiasis due to risk of exacerbation from transient hypercalcemia 4
• Discontinue if worsening of previously stable cutaneous calcification develops 4

Administration Technique and Initial Dosing Protocol

Injection Training

• Patients must learn self-administration of 20 mcg subcutaneously once daily into the thigh or abdominal region 4
• Administer the first several doses under circumstances where the patient can sit or lie down if symptoms of orthostatic hypotension occur, as transient orthostatic hypotension may develop with initial doses 4
• The pen injection device is generally well-accepted, with patient concerns about injection discomfort decreasing from 42% at baseline to minimal levels by 6 months 5

Calcium and Vitamin D Management

• Limit total daily calcium intake to 1500 mg from both supplements and dietary sources, combined with adequate vitamin D intake (≤1000 IU/day) 6
• Consider supplemental calcium and vitamin D based on individual patient needs, but excessive calcium increases hypercalcemia risk 4, 6

Monitoring Requirements

Baseline Assessment

• Obtain serum calcium level at baseline to exclude underlying hypercalcemic disorders 4
• Document baseline bone mineral density and fracture history to establish treatment response benchmarks 1

Follow-up Monitoring

• Check serum calcium after 1 month of treatment (>16 hours after previous dose); this single measurement is sufficient for most patients 6, 5
• If mild hypercalcemia develops, manage by withdrawing dietary calcium supplements, reducing dosing frequency, or both 6
• Five patients in one study had mildly elevated calcium (maximum 2.8 mmol/L) at 3 months, but all normalized on repeat testing approximately 4 weeks later 5

Expected Adverse Effects

Common Side Effects (>10%)

• Arthralgia, pain, and nausea are the most common adverse reactions 4
• Dizziness (10.3%), nausea (10.3%), back pain (7.8%), and muscle cramps (7.8%) were reported in clinical studies 5
• Teriparatide probably increases withdrawal due to adverse effects (moderate certainty), most commonly nausea, dizziness, vomiting, and leg cramps 1, 3

Serious Adverse Events

• Teriparatide may increase serious adverse events compared to placebo (moderate certainty evidence) 3

Treatment Duration and Sequential Therapy Algorithm

Maximum Treatment Duration

• Limit teriparatide to 24 months during a patient's lifetime 1, 2, 4
• Use beyond 2 years should only be considered if the patient remains at or has returned to very high fracture risk 3, 4

Mandatory Sequential Therapy

• Patients MUST transition to antiresorptive therapy (bisphosphonates or denosumab) immediately after completing teriparatide to preserve bone density gains and prevent rebound vertebral fractures 1, 2, 3
• Discontinuation without follow-up antiresorptive therapy results in rapid bone loss 2
• This sequential therapy requirement is a critical component of the treatment plan that must be discussed upfront 7

Drug Interactions and Concurrent Medications

Avoid Concurrent Bisphosphonates

• Do not initiate teriparatide and bisphosphonates together in previously untreated patients, as concurrent use may reduce the anabolic response to teriparatide 8, 6
• Pretreating patients for a short time with alendronate before initiating teriparatide may also somewhat reduce the anabolic response 8

Digoxin Interaction

• Transient hypercalcemia may predispose patients to digitalis toxicity in patients taking digoxin 4

Special Population Considerations

Pregnancy and Lactation

• Consider discontinuing teriparatide when pregnancy is recognized 4
• Breastfeeding is not recommended during teriparatide therapy 4

Women of Childbearing Potential

• For women of childbearing potential at high fracture risk, teriparatide is second-line after oral bisphosphonates 7
• Teriparatide is preferred over IV bisphosphonates or denosumab in this population due to better safety profile if unplanned pregnancy occurs 7

Glucocorticoid-Induced Osteoporosis

• Teriparatide is indicated for men and women with osteoporosis associated with sustained systemic glucocorticoid therapy at high risk for fracture 4
• Moderate-quality evidence supports teriparatide use in patients taking glucocorticoids 3

Cost and Access Considerations

Financial Burden

• Teriparatide is the most expensive osteoporosis treatment at $22,156 average annual cost per Medicare beneficiary, approximately 4-fold more expensive than romosozumab ($5,574) 1
• The high acquisition cost means teriparatide should be reserved for patients with severe osteoporosis at very high fracture risk or those who have failed other therapies 9

Patient Selection Criteria

Appropriate Candidates

• Postmenopausal women with osteoporosis at high risk for fracture (mean age >74 years) who have failed or are intolerant to other available osteoporosis therapy 1, 4
• Men with primary or hypogonadal osteoporosis at high risk for fracture or who have failed or are intolerant to other therapies 1, 4
• Patients with recent fracture (within past 12 months), history of multiple clinical osteoporotic fractures, T-score ≤-3.5, or failure of other available osteoporosis therapies 2, 8

Not First-Line Therapy

• Bisphosphonates remain first-line therapy due to more favorable balance among benefits, harms, patient values and preferences, and cost 1
• Teriparatide should never be used as first-line therapy and is reserved exclusively for severe osteoporosis 3