High fracture risk osteoporosis drug

Synopsis of major recommendations to the clinician

These recommendations apply to postmenopausal women and men aged 50 years and older.

Universal recommendations

• Counsel individual patients on their risk for osteoporosis, fractures, and potential consequences of fractures (functional deterioration, loss of independence, increased mortality).
• Recommend a diet with adequate total calcium intake (1000 mg/day for men aged 50–70 years; 1200 mg/day for women ≥ 51 years and men ≥ 71 years), incorporating calcium supplements if intake is insufficient.
• Monitor serum 25-hydroxyvitamin D levels.
• Maintain serum vitamin D sufficiency (≥ 30 ng/mL but below ≤ 50 ng/mL). Prescribe supplemental vitamin D (800–1000 units/day) as needed for individuals aged 50 years and older to achieve a sufficient vitamin D level. Higher doses may be necessary in some adults, especially those with malabsorption. (Note: in healthy individuals a serum 25(OH) vitamin D level ≥ 20 ng/mL may be sufficient, but in the setting of known or suspected metabolic bone disease ≥ 30 ng/mL is appropriate.)
• Identify and address modifiable risk factors associated with falls, such as sedating medications, polypharmacy, hypotension, gait or vision disorders, and out-of-date prescription glasses.
• Provide guidance for smoking cessation, and avoidance of excessive alcohol intake; refer for care as appropriate.
• Counsel or refer patients for instruction on balance training, muscle-strengthening exercise, and safe movement strategies to prevent fracture(s) in activities of daily life.
• In community-dwelling patients, refer for at-home fall hazard evaluation and remediation.
• In post-fracture patients who are experiencing pain, prescribe over-the-counter analgesia, heat/ice home care, limited bed rest, physical therapy, and alternative non-pharmacologic therapies when appropriate. In cases of intractable or chronic pain, refer to a pain specialist or physiatrist.
• Coordinate post-fracture patient care via fracture liaison service (FLS) and multidisciplinary programs in which patients with recent fractures are referred for osteoporosis evaluation and treatment, rehabilitation, and transition management.

Diagnostic assessment recommendations

• Investigate any broken bone in adulthood as suspicious for osteoporosis , regardless of cause.
• Measure height annually, preferably with a wall-mounted stadiometer (without shoes).
• Record history of falls.
• Perform BMD testing in the following:
• –Women aged ≥ 65 years and men aged ≥ 70 years.
• –Postmenopausal women and men aged 50–69 years, based on risk profile.
• –Postmenopausal women and men aged ≥ 50 years with history of adult-age fracture.
• –DXA facilities that employ accepted quality assurance measures.
• –The same facility and on the same densitometry device for each test whenever possible.
• Maintain diagnosis of osteoporosis in patient diagnosed by fracture in adulthood or T-score (− 2.5 or below), even if subsequent DXA T-score is above − 2.5.
• To detect subclinical vertebral fractures, perform vertebral fracture imaging (X-ray or DXA vertebral fracture assessment) in the following:
• –Women aged 65 years and older if T-score is less than or equal to − 1.0 at the femoral neck.
• –Women aged 70 years or older and men aged 80 years or older if T-score is less than or equal to − 1.0 at the lumbar spine, total hip, or femoral neck.
• –Men aged 70–79 years if T-score is less than or equal to − 1.5 at the lumbar spine, total hip, or femoral neck.
• –Postmenopausal women and men aged ≥ 50 years with the following specific risk factors:
• ○Fracture(s) during adulthood (any cause).
• ○Historical height loss of ≥ 1.5 in. (defined as the difference between the current height and peak height).
• ○Prospective height loss of ≥ 0.8 in. (defined as the difference between the current height and last documented height measurement).
• ○Recent or ongoing long-term glucocorticoid treatment.
• ○Diagnosis of hyperparathyroidism.
• Rule out secondary causes of bone loss, osteoporosis, and/or fractures.
• In appropriate untreated postmenopausal women, selectively measure bone turnover markers to help gauge rapidity of bone loss.
• Prior to elective orthopedic procedures, evaluate skeletal health and measure BMD as indicated by risk profile (e.g., inflammatory arthritis, osteoarthritis, chronic kidney disease, or adverse events from surgery or other risk factors).

Pharmacologic treatment recommendations

• No uniform recommendation applies to all patients. Management plans must be individualized.
• Current FDA-approved pharmacologic options for osteoporosis are as follows:
• –Bisphosphonates (alendronate, ibandronate, risedronate, zoledronic acid)
• –Estrogen-related therapy (ET/HT, raloxifene conjugated estrogens/ bazedoxifene)
• –Parathyroid hormone analogs (teriparatide, abaloparatide)
• –RANK-ligand inhibitor (denosumab)
• –Sclerostin inhibitor (romosozumab)
• –Calcitonin salmon
• Consider initiating pharmacologic treatment in postmenopausal women and men ≥ 50 years of age who have the following:
• –Primary fracture prevention:
• ○T-score ≤ − 2.5 at the femoral neck, total hip, lumbar spine, 33% radius (some uncertainty with existing data) by DXA.
• ○Low bone mass (osteopenia: T-score between − 1.0 and − 2.5) at the femoral neck or total hip by DXA with a 10-year hip fracture risk ≥ 3% or a 10-year major osteoporosis-related fracture risk ≥ 20% (i.e., clinical vertebral, hip, forearm, or proximal humerus) based on the US-adapted FRAX® model.
• –Secondary fracture prevention:
• ○Fracture of the hip or vertebra regardless of BMD.
• ○Fracture of proximal humerus, pelvis, or distal forearm in persons with low bone mass (osteopenia: T-score between − 1.0 and − 2.5). The decision to treat should be individualized in persons with a fracture of the proximal humerus, pelvis, or distal forearm who do not have osteopenia or low BMD.
• Initiate antiresorptive therapy following discontinuation of denosumab, teriparatide, abaloparatide, or romosozumab.

Monitoring patients and treatment response

• Perform BMD testing 1 to 2 years after initiating or changing medical therapy for osteoporosis and at appropriate intervals thereafter according to clinical circumstances.
• –More frequent BMD testing may be warranted in higher-risk individuals (multiple fractures, older age, very low BMD).
• –Less frequent BMD testing may be warranted as follow-up for patients with initial T-scores in the normal or slightly below normal range (osteopenia) and for patients who have remained fracture free on treatment.
• In patients receiving osteoporosis pharmacologic treatment:
• –Routinely reassess risk for fracture, patient satisfaction and adherence with therapy, and need for continued or modified treatment. The appropriate interval between initiation and reassessment differs with agent prescribed.
• –Serially measure changes in BMD at lumbar spine, total hip, or femoral neck; if lumbar spine, hip, or both are not evaluable or according to clinical judgment, consider monitoring at 33% distal radius.
• –Reassess patient and BMD status for consideration of a drug holiday after 5 years of oral and 3 years of intravenous bisphosphonate in patients who are no longer at high risk of fracture (T-score ≥ − 2.5, no new fractures).
• –At each healthcare encounter, ask open-ended questions about treatment to elicit patient feedback on possible side effects and concerns. Communicate risk-benefit trade-offs and confirm understanding: both the risk of adverse events with treatment (usually very low) and risk of fractures and their negative consequences without treatment (usually much higher).

Osteoporosis: impact and overview

Osteoporosis is a disease characterized by low bone density, deterioration of bone tissue, disrupted bone microarchitecture, compromised bone strength, and fracture. According to the World Health Organization (WHO) diagnostic classification, osteoporosis is defined by BMD at the hip or lumbar spine that is less than or equal to 2.5 standard deviations below the mean BMD of a young adult reference population (T-score).

Osteoporosis is a risk factor for fracture, just as hypertension is for stroke and hypercholesterolemia is for heart disease. While risk is highest in individuals with extremely low BMD, the majority of fractures occur in patients with T-scores better than − 2.5. Non-BMD factors contribute to fracture risk, such as falls, frailty, and poor bone quality.

Scope of the problem

Osteoporosis affects an enormous number of people, both men and women, of all races. Among Caucasian adults in the USA aged 50 years and older, about 50% of women and 20% of men will experience an osteoporotic fracture in their remaining lifetime. Rates of fracture differ by ethnic/racial population and skeletal site.

For fracture at any site in women, after adjusting for BMD, weight, and other covariates, non-Hispanic white and Hispanic-American women have the highest risk for fracture, followed by Native Americans, African Americans, and Asian Americans. For hip fracture in men, the age-adjusted incidence was highest for non-Hispanic white men, similar among Hispanic-American and black men, and lowest in Asian men.

In a 2014 cross-sectional analysis of data from five large independent cohorts (in the USA and Asia), prevalence of self-reported non-traumatic fracture in men was non-Hispanic white American 17.1%; Afro-Caribbean, 5.5%; African American, 15.1%; Hispanic-American, 13.7%; Asian American, 10.5%; Hong Kong Chinese, 5.6%, and Korean, 5.1%.