Primary and Secondary Osteoporosis Prevention: Fracture Risk Groups and Treatment Recommendations

Key Takeaways

• Patients older than 50 years of age who are at a high or very high risk of fracture should consider pharmacotherapy for primary prevention.
• Patients with a history of fracture and those at risk for further fractures should receive pharmacotherapy for secondary prevention.
• Calcium, vitamin D, and exercise are equally important to help patients maintain bone health and have a healthy lifestyle as they age.

Introduction
Osteoporosis is considered a major public health problem and is becoming increasingly prevalent. Therefore, it is important to discuss primary and secondary osteoporosis prevention. Numerous factors contribute to osteoporosis and fracture risk. Skeletal risk factors include low bone mineral density (BMD), previous fractures, high bone turnover, or a family history of osteoporosis. Nonskeletal risk factors include age, poor eyesight, poor hearing, poor balance, and muscle weakness. Some nonskeletal risk factors can be treated by reducing fall risk, providing hip protectors, and giving vitamin D and calcium supplements. However, skeletal risk factors require treatment with bone-active agents.

The Importance of Risk Factors: The NORA Study
We often think that patients need low BMD (T-score of -2.5 or less) before they are at an increased risk of fracture, but many years ago in the NORA study, nearly 150,000 postmenopausal White women 50-104 years of age were screened for osteoporosis and prevalent fractures. What was interesting—and even paradigm shifting—was that most fractures occurred in women who had T-scores above -2. So, BMD is important, but so are other risk factors when it comes to determining fracture risk.

Whom to Treat for Osteoporosis
In 2014, the National Osteoporosis Foundation provided guidance on treating osteoporosis, and in 2020, the American Association of Clinical Endocrinology (AACE) provided new recommendations. Per the updated recommendations, after excluding secondary causes, osteoporosis treatment should be initiated in postmenopausal women and men who are 50 years of age or older if they have a spine or hip fracture or if they have a BMD by dual-energy x-ray absorptiometry (DXA) T-score of -2.5 or less at the spine, femoral neck, total hip, and—now—one third distal radius.

If a patient has osteopenia or low bone mass, we look at a BMD by DXA T-score between -1 and -2.5, and then we apply the Fracture Risk Assessment Tool (FRAX) 10‑year fracture risk assessment to determine if patients have a 10‑year fracture risk of >3% at the hip or >20% for a major osteoporotic‑related fracture. Treatment is then recommended.

AACE Guidelines

High-Risk Fracture Group
The AACE guidelines provide additional steps for the management of osteoporosis based on patient fracture risk. The guidelines define a patient as having a high fracture risk if they have a T-score between -1 and -2.5, a history of fracture, a T-score below -2.5 in numerous locations, or a FRAX showing a 10-year risk of major fracture >20% or a hip fracture risk of 3%. Such patients require initial treatment with an antiresorptive agent and should have a DXA reassessment every 1-2 years, and their clinical management will depend on BMD and fracture risk category.

Very High–Risk Fracture Group
The AACE guidelines also have gone further in the management of osteoporosis to identify a very high–risk fracture group. Who are these patients? They are patients who fractured within 1 year, fractured while receiving osteoporosis therapy, have had multiple fractures, are receiving medications such as glucocorticoids that cause skeletal harm, or have T-scores below -3. These patients are at increased risk for a fall, and their FRAX scores are very high, with a major osteoporotic fracture risk over 10 years of >30% or hip fracture >4.5%.

How do we treat these patients? Initial therapy should be an anabolic agent or an injectable antiresorptive agent, and then the patient should be reassessed every 1‑2 years by DXA. Patients who started on antiresorptive therapy may benefit by switching to an anabolic therapy.

In general, we want to be more aggressive in our treatment of this very high–risk group to lower their fracture risk.

Treatment Recommendations
Pharmacotherapy available for treating osteoporosis includes bisphosphonates, the anti-RANK ligand denosumab, the hormone-related therapy raloxifene, the antisclerostin dual-action agent romosozumab, and the anabolic agents parathyroid hormone teriparatide and parathyroid hormone–related peptide abaloparatide.

The AACE guidelines now recommend denosumab and bisphosphonates as initial therapy for high-risk patients. For very high–risk patients, abaloparatide, teriparatide, an injectable bisphosphonate, zoledronate, denosumab, or the dual-action romosozumab are recommended. Although ibandronate and raloxifene do improve bone mass and decrease incident spine fractures, they were unable to demonstrate any reduction in hip fractures in randomized, controlled trials.

In addition, the American Society for Bone and Mineral Research established a task force and issued recommendations for secondary osteoporosis prevention. To prevent the risk of further fracture, these guidelines strongly emphasize the need to provide pharmacologic therapy for patients aged 65 or older who have had a hip or vertebral fracture. SC denosumab, IV zoledronic acid, alendronate, and risedronate are recommended as first-line therapies. To prevent subsequent fractures, patients should receive a minimum of 800 IU of vitamin D and 1200 mg of calcium in their diet per day.

In postmenopausal women, all FDA-approved drugs are effective in reducing vertebral fractures. However, for glucocorticoid-induced osteoporosis or osteoporosis in men, only risedronate, zoledronate, denosumab, teriparatide, and abaloparatide have indications for treatment. Studies have shown that alendronate, zoledronate, and denosumab have benefit in reducing hip fractures, whereas calcitonin, raloxifene, and ibandronate have not been shown to be effective. Currently, there are no data available on the effectiveness of the anabolic agents and romosozumab for hip fractures.

So, when we think about a patient in terms of their fracture risk, we can take a stepwise approach to therapy. For women older than 50 years of age who are otherwise healthy, we recommend calcium, vitamin D, and exercise. As patients become higher risk, we recommend bisphosphonates. And for those who are very high risk, we recommend either the anti‑RANK ligand antibody denosumab, the parathyroid hormone compounds, or the antisclerostin antibody, because these are all effective therapies for patients who are very high risk for osteoporosis or who have already experienced a fracture.

Supplementation
As we think about supplements, we should remember that calcium intake is the cornerstone of all bone health interventions. Patients older than 50 years of age should get 1200 mg of calcium per day. The usual American diet provides approximately 700-900 mg of calcium per day and should be supplemented up to 1200 mg based on individual patient intake. Increasing calcium intake above 1200 mg has not been shown to provide additive benefits and actually may be detrimental. A vitamin D level should be between 30 and 50 ng/mL, which is achievable with vitamin D supplements of 1000-2000 IU per day. Patients should avoid taking >4000 IU per day, as there is no added benefit and this can cause unintended consequences.

Patient Education
We should always emphasize patient education, as patients can have a significant impact on improving their bone health. Educate patients on how to lower their osteoporotic fracture risk and maintain their bone health with supplementation with calcium and vitamin D as needed. Dietary intake of calcium should be encouraged if tolerated. Patients also should be advised to do weight-bearing and balance-resistance exercises and should avoid smoking or drinking alcohol. Finally, patients should be educated on how to prevent falls at home. Encourage physical therapy if needed, as muscle strengthening and improving balance by itself reduces falls.

Conclusion
Patients older than 50 years of age who are at a high or very high risk of fracture should consider pharmacotherapy for primary prevention. Patients with a history of fracture and those at risk for further fractures should receive pharmacotherapy for secondary prevention. Calcium, vitamin D, and exercise are equally important, as they help patients maintain bone health and have a healthy lifestyle as they age.

Your Thoughts?
In your practice, what recommendations or suggestions do you provide to patients to maintain bone health? Answer the polling question and join the discussion by posting a comment.