Osteoporosis Treatment for Postmenopausal Women at High Risk for Fracture

SUMMARY:

The Endocrine Society released guidance (2019) on the pharmacological management of osteoporosis and, based on evidence, recommends

…treating postmenopausal women at high risk of fractures, especially those who have experienced a recent fracture, with pharmacological therapies, as the benefits outweigh the risks

Definition of High Risk

Definition of high risk
- Prior spine or hip fracture or
- BMD T-score of ≤−2.5 either the hip or spine or
- 10-year hip fracture risk ≥3% or
- Risk of major osteoporotic fracture ≥20%

Treatment Options

Initial treatment for women at high risk of fractures: Bisphosphonates
- Alendronate | Risedronate | Zoledronic acid | Ibandronate
- Reassess fracture risk at 3 to 5 years
- High risk should continue therapy while low-to-moderate risk may be candidates for ‘bisphosphonate holiday’
- Ibandronate not recommended for nonvertebral or hip fracture risk reduction

Note: Osteonecrosis of the jaw (ONJ) and bisphosphonates: Absolute risk ranges from 1 in 10,000 to 1 in 100,000 | Higher risk in oncology setting | Risk may be as high as 21 in 10,000 if on medication >4 years | Increased risk with tooth extraction (0.5%)

Alternative initial treatment: Denosumab
- 60 mg subcutaneously every 6 months
- Reassess risk at 5 to 10 years as to whether patient should remain on denosumab
Consider SERMs (raloxifene or bazedoxifene)
- Low risk of DVT and bisphosphonates/ denosumab not appropriate or
- High risk of breast cancer
Consider menopausal hormone therapy (estrogen only for women with hysterectomy) if
- Cannot tolerate bisphosphonates/ denosumab or bisphosphonates/ denosumab not appropriate
- <60 years of age or <10 years beyond menopause
- Low risk of deep vein thrombosis | No contraindications | No previous history of MI or stroke | No breast cancer
- Symptomatic vasomotor symptoms and/or other menopausal symptoms
- Note ACP Guidelines disagree on the use of HRT in osteoporosis

Note: Tibolone may used based on the above clinical scenarios as well | Tibolone not currently available in the US or Canada)

In women >60 who cannot tolerate bisphosphonates/ denosumab or bisphosphonates/ denosumab not appropriate, consider the following (in order)
- SERM
- HT or tibolone
- Calcitonin
- Calcium and vitamin D

Very High Risk of Fracture

Severe osteoporosis (i.e., low BMD T-score <−2.5 and fractures) or multiple vertebral fractures

Teriparatide and abaloparatide
- These medications are parathyroid hormone and parathyroid hormone–related protein analogs
- Anabolic agents that increase bone formation
- Recommended for up to 2 years
- Follow up using antiresorptive osteoporosis therapies to maintain gains
Romosozumab
- Monoclonal antibody that blocks sclerostin and increases new bone formation
- Recommended for up to 1 year
- Recommended dosage is 210 mg monthly by subcutaneous injection
- Following course of romosozumab, treat with antiresorptive osteoporosis therapies to maintain bone mineral density gains and reduce fracture risk

Note: Women at high risk of cardiovascular disease (e.g., MI or stroke) should not be considered for romosozumab

KEY POINTS:

Calcitonin (nasal spray) may be an option only if patients cannot tolerate or should not be prescribed the following
- Raloxifene | Bisphosphonates | Estrogen | Denosumab | Tibolone | Abaloparatide | Teriparatide
Calcium and vitamin D
- Suggested adjunct to above therapies
- Recommended supplementation even if women cannot tolerate other pharmacologic therapy
Monitoring
- Bone mineral density
  - Dual-energy X-ray absorptiometry at the spine and hip
  - Perform every 1 to 3 years
  - Note ACP guidelines recommend against DEXA scans during 5 years of pharmacological treatment
- Bone turnover (alternative to determine poor response or treatment nonadherence)
  - Serum C-terminal crosslinking telopeptide for antiresorptive therapy or
  - Procollagen type 1 N-terminal propeptide for bone anabolic therapy
Good bone health maintenance efforts are recommended for all postmenopausal women and include
- Adequate calcium and vitamin D intake
- Resistance and balance exercises
- Smoking cessation
- Limited alcohol use
- Decreased use of drugs
- Optimization of comorbid conditions that can harm bone
When choosing the best therapy
- Multiple factors (e.g., costs, patient preferences, local guidance and drug availability etc.) will guide care
- Individualize approach based on personalized risk/benefit

Learn More – Primary Sources:

Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society Clinical Practice Guideline

Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society Guideline Update

FDA approves new treatment for osteoporosis in postmenopausal women at high risk of fracture

USPSTF Recommendations: Screening for Osteoporosis to Prevent Fractures

SUMMARY:

The USPSTF released recommendations update for osteoporosis screening to prevent fractures (2018). The following guidelines are based upon an assessment of benefits vs harms and does not include cost analysis.

USPSTF Recommendations
Clinical risk factors in postmenopausal women <65 years of age
Clinical risk assessment tools
Screening Tests
Additional Related USPSTF Recommendations
Other Professional Recommendations

USPSTF Recommendations

Women ≥ 65 years and older

The USPSTF recommends screening for osteoporosis with bone measurement testing to prevent osteoporotic fractures (B recommendation)
- Offer or provide this service
- There is high certainty that the net benefit is substantial

Women <65 years and postmenopausal

The USPSTF recommends screening for osteoporosis with bone measurement testing to prevent osteoporotic fractures in women who are at increased risk, as determined by a formal clinical risk assessment tool (B recommendation)
- Offer or provide this service
- There is high certainty that the net benefit is substantial
The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for osteoporosis to prevent osteoporotic fractures in men (I statement)
- The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the service
- Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined

KEY POINTS:

Clinical Risk Factors in Postmenopausal Women <65 Years of Age

If ≥1 risk factor, “a reasonable approach” is to use a clinical risk assessment tool (see below)
Clinical risk factors include
- Parental history of hip fracture
- Smoking
- Excessive alcohol consumption
- Low body weight

Clinical risk assessment tools

In the previous guideline (2011), FRAX was the clinical risk assessment tool of choice
- Current (2018) guidance now includes others
The following tools perform similarly and are moderately accurate at predicting osteoporosis
- The Simple Calculated Osteoporosis Risk Estimation (SCORE)
- Osteoporosis Risk Assessment Instrument (ORAI)
- Osteoporosis Index of Risk (OSIRIS)
- Osteoporosis Self-Assessment Tool (OST)
FRAX tool (University of Sheffield)
- Assesses a person’s 10-year risk of fracture
- Includes questions about previous DXA results but not required to assess risk

USPSTF states that one approach is to

Perform bone measurement testing in postmenopausal women younger than 65 years who have a 10-year FRAX risk of major osteoporotic fracture (without DXA) greater than that of a 65-year-old white woman without major risk factors
Example, using white woman of mean height and weight
- 65-year-old without major risk factors: 10-year FRAX risk of major osteoporotic fracture of 8.4%
- 60-year-old with a parental history of hip fracture: 10-year FRAX risk of major osteoporotic fracture of 13%
A particular risk factor or a certain age does not represent a particular risk threshold
Multiple risk factors at a younger age may indicate that the risk-benefit profile is favorable for screening with bone measurement testing

Screening Tests

Central DXA (most common)
- Measures BMD at the hip and lumbar spine
- Used for most professional treatment guidelines (based on entry criteria for study enrollment)
Peripheral DXA
- Measures BMD at the lower forearm and heel
- Due to portable device measurement, may provide access when central DXA is not available
Quantitative ultrasound (QUS)
- Evaluates peripheral sites
- Similar accuracy in predicting fracture risk as DXA
- Avoids radiation exposure
- Does not measure BMD and therefore prior to routine use, a conversion method to the DXA scale is needed

Additional Related USPSTF Recommendations

Preventing falls
- The USPSTF recommends exercise interventions to prevent falls in community-dwelling adults 65 years and older at increased risk of falls
- Selectively offer multifactorial interventions based on circumstances of prior falls, presence of comorbid medical conditions, and the patient’s values and preferences
- USPSTF recommends against Vitamin D supplementation to prevent falls
Preventing fractures
- USPSTF recommends against supplementation with 400 IU or less of vitamin D and 1000 mg or less of calcium in postmenopausal women to prevent fractures
- The USPSTF found insufficient evidence on supplementation with higher doses of vitamin D and calcium, alone or combined, to prevent fractures in postmenopausal women, or at any dose in men and premenopausal women

Other Professional Recommendations

National Osteoporosis Foundation
- Recommends BMD testing in all women 65 years and older and all men 70 years and older
- Recommends BMD testing in postmenopausal women younger than 65 years and men aged 50 to 69 years based on their risk factor profile, including if they had a fracture as an adult
The International Society for Clinical Densitometry
- Recommends BMD testing in all women 65 years and older and all men 70 years and older
- Recommends BMD testing in postmenopausal women younger than 65 years and men younger than 70 years who have risk factors for low bone mass
American Academy of Family Physicians (as part of Choosing Wisely)
- Recommends against DXA screening in women younger than 65 years and men younger than 70 years with no risk factors
ACOG
- Recommends BMD testing with DXA in postmenopausal patients 65 years and older
- Recommends selective screening in postmenopausal women younger than 65 years who have osteoporosis risk factors as determined by formal clinical risk assessment tool
American Association of Clinical Endocrinologists
- Recommends evaluating all women 50 years and older for osteoporosis risk and considering BMD testing based on clinical fracture risk profile
Endocrine Society
- Recommends screening in men older than 70 years
- Recommends screening adults
  - 50 to 69 years with significant risk factors
  - Fracture after age 50 years