CMS250 - Week 12

Osteopenia and Osteoporosis

• Osteopenia and osteoporosis are conditions characterized by decreased bone mineral density, increasing the risk of fractures.

Osteoporosis Definition

• Osteoporosis translates to "porous bone".
• It involves decreased bone mineral density (BMD) below normal reference values.
• WHO defines osteoporosis as a T-score less than -2.5.
• Reduced bone mass and strength, typically in trabecular bone, lead to higher fracture rates.

Osteopenia Definition

• Osteopenia is a precursor to osteoporosis.
• It involves decreased bone mineral density (BMD) below normal reference values, though not enough to meet osteoporosis diagnostic criteria.
• WHO defines osteopenia as a T-score between -1 and -2.5.

Peak Bone Mass

• Peak bone mass is typically achieved by age 30.
• 80% of peak bone mass is determined by genetic/heritable factors.
• Weight-bearing exercises, adequate calcium and vitamin D intake, body mass, and hormonal balance are modifiable factors.

Primary Osteoporosis

• Primary osteoporosis is caused by gradual and natural bone loss with aging and postmenopausal estrogen deficiency.
• After age 30, bone resorption exceeds bone formation.
• Bone mass decline happens at a rate of ~0.4% each year.
• In women without hormone therapy, the rate of decline increases to 2-5% per year for the first 5-10 years of menopause, then slows to a decline of 1% per year.

Secondary Osteoporosis

• Secondary osteoporosis results from other diseases or medications.
• Medical conditions include: hyperparathyroidism, anorexia, malabsorption syndromes, hyperthyroidism, chronic renal failure, hypogonadism, amenorrhea/oligomenorrhea, early onset menopause, and chronic conditions resulting in calcium and/or vitamin D deficiencies.
• Medications: excess glucocorticoids, long-term steroid use, valproic acid, proton pump inhibitors, antiepileptics, and chemotherapy agents.

Osteoporosis-Related Fractures

• Osteoporosis predisposes individuals to low-impact fragility fractures which lead to a significant decline in quality of life, increasing morbidity, mortality, and disability.
• Common fracture sites include: vertebrae, hip (femoral neck), and wrists.
• These fractures result from a fall from standing height or lower.
• Fractures due to major trauma or those at non-osteoporotic sites, such as hands/fingers, feet/toes, face, and skull are excluded.
• Lifetime risk of osteoporotic fracture is 50% for a 50-year-old Caucasian woman and 25% for a 50-year-old Caucasian man.

Osteoporosis-Related Fractures Burden of Disease

• Over 2 million fractures per year are related to osteoporosis, including ~300,000 hip fractures and 700,000 vertebral fractures.
• Clinical fracture is associated with a 2x increase in mortality risk.
• The overall mortality rate in the first year after hip fracture (at femoral neck) is 20%.
• Men with a hip fracture have a higher mortality rate than women in general.
• Only ~40% of those with femoral neck fracture can return to their pre-fracture level of independence.
• ~30% of patients lose their independence and require nursing home care.
• Full recovery is rare and overall quality of life is poor.
• Many patients develop secondary complications such as pressure sores, deep vein thrombosis, and nosocomial infections while hospitalized for hip fracture.

Osteopenia/Osteoporosis Epidemiology

• Females have a 4x higher overall prevalence of osteopenia/osteoporosis compared to males.
• White and Hispanic women are more commonly affected, followed by Native American, Asian, and Black women.
• Males are more likely to demonstrate secondary causes of decreased bone mass.
• Approximately 2.2 million Canadians >40 years of age have diagnosed osteoporosis.
• Prevalence in the United States: 15.4% of women aged 50 and older, 4.3% of men aged 50 and older, 25% in women aged 65 and older, and 5.6% in men aged 65 and older.
• 54% of postmenopausal women are osteopenic, while an additional 30% are considered osteoporotic.
• By age 80, 27% of women are osteopenic and 70% are considered osteoporotic.
• Worldwide, Asia has reported the lowest average T-scores by region.

Osteopenia/Osteoporosis Risk Factors

• Major risk factors: age >65 years, low bone mineral density, ethnicity (white, Asian, Hispanic), personal history of fracture (vertebral compression fracture, fragility fracture after age 40), family history of osteoporosis or osteoporotic fracture, systemic glucocorticoid therapy for >3 months, malabsorption syndrome, primary hyperparathyroidism, propensity to fall, osteopenia apparent on radiography, hypogonadism, and early menopause (before age 45).
• Minor risk factors: rheumatoid arthritis, history of clinical hyperthyroidism, chronic anticonvulsant therapy, low dietary calcium intake, smoker, excessive alcohol intake (3 or more alcoholic drinks/day), excessive caffeine intake, weight <57 kg, >10% weight loss at age 25, chronic heparin therapy, and aromatase inhibitors.

Osteoporosis-Related Fractures Risks

• Low bone mineral density is the strongest risk factor for fracture.
• Conditions associated with increased risk of fractures: age ≥65 years.
• Additional conditions for men aged 50-64 and postmenopausal women: parent with hip fracture, osteopenia identified on X-ray, current smoking, excessive alcohol intake, and low body weight (<60 kg) or major weight loss (>10% of weight since age 25).
• History of fragility fracture, hypogonadism or premature menopause (<45 years), and secondary osteoporosis (hyperthyroidism, Cushing syndrome, hyperparathyroidism, renal disease, organ transplantation, GI diseases, other disorders associated with rapid bone loss or fracture like rheumatoid arthritis and multiple myelomas) are risks at any age.
• Medications associated with increased fracture risk: androgen deprivation therapy, loop diuretics, anticoagulants (unfractionated and low molecular weight heparins, warfarin), proton pump inhibitors (PPIs), antiepileptic drugs (valproic acid and enzyme inducers), selective serotonin reuptake inhibitors (SSRIs), antiretroviral therapy, thiazolidinediones, aromatase inhibitors, Vitamin A (high dose), chemotherapy, corticosteroids (prolonged use), cyclosporine, and drugs associated with increased risk of falls in the elderly (e.g., antipsychotics, sedatives).

Osteopenia/Osteoporosis Symptoms and Signs

• Typically asymptomatic.
• Obtain a comprehensive history to elicit potential risk factors attributable to secondary bone loss.
• Obtain a thorough social history, noting attention to smoking, alcohol consumption, and family history of osteoporosis and fractures.
• Physical exam is normal except in certain cases of advanced disease states.
• These cases include: back/bone pain, loss of height, and kyphosis from vertebral fractures.

Accuracy of Physical Exam Findings

• No single finding is sufficient to rule in or rule out osteoporosis or spinal fracture without further testing.
• A weight less than 51kg has a sensitivity of 22% and specificity of 97% for diagnosing osteoporosis.
• A tooth count less than 20 has a sensitivity of 27% and specificity of 92% for diagnosing osteoporosis.
• Self-reported humped back has a sensitivity of 20.6% and specificity of 97% for diagnosing osteoporosis.
• Wall-occiput distance greater than 0 cm has a sensitivity of 60% and specificity of 87% for spinal fracture diagnosis.
• Rib-pelvis distance less than 2 finger breadths has a sensitivity of 88% and specificity of 46% for spinal fracture diagnosis.
• Armspan-height difference greater than 5 cm has a sensitivity of 39% and specificity of 76% for spinal fracture diagnosis.

Osteopenia/Osteoporosis Diagnosis

• Bone mineral density (BMD) is assessed via dual-energy x-ray absorptiometry bone scans (DXA or DEXA bone densitometry).
• This is considered the gold standard established by the World Health Organization (WHO).
• Decreasing BMD values reflect an underlying disruption in the microarchitecture of bone.

Indications for Measuring BMD

• For older adults (Age ≥ 50 Years): Age ≥ 65 years (both men and women); clinical risk factors for fracture (menopausal women, men aged 50-64 years); fragility fracture after age 40 years; prolonged use of glucocorticoids; use of other high-risk medications; parental hip fracture; vertebral fracture or osteopenia identified on radiography; current smoking; high alcohol intake; low body weight (< 60 kg) or major weight loss (>10% of body weight at age 25 years); rheumatoid arthritis; and other disorders strongly associated with osteoporosis.
• For younger adults (Age < 50 Years): Fragility fracture; prolonged use of glucocorticoids; use of other high-risk medications; hypogonadism or premature menopause (age < 45 years); malabsorption syndrome; primary hyperparathyroidism; and other disorders strongly associated with rapid bone loss and/or fracture.

DXA/DEXA Scans

• Lumbar spine (L2-L4), hip (femoral neck, trochanters, intertrochanteric regions), and wrist are routinely included in the scan.
• BMD is reported in grams of mineral per area and volume of bone, reflecting the absolute, patient-specific score from the measured anatomic areas.
• Reports include T-scores and Z-scores.

DXA/DEXA Scans T-scores

• T-score measures standard deviations between the patient's measured BMD and the mean BMD in healthy, young, matched controls of the same sex at peak bone mass (~25-30-year-olds).
• WHO criteria for bone disease based on BMD: Normal BMD: T-score between +2.5 and -1.0; Osteopenia: T-score between -1.0 and -2.5; Osteoporosis: T-score at or below -2.5; Severe osteoporosis: T-score at or below -2.5 with one or more fragility fractures.

DXA/DEXA Scans Z-scores

• Z-score measures standard deviations between the patient's measured BMD and the mean BMD in healthy, age-matched controls.
• A Z-score below -1.5 warrants a comprehensive secondary osteoporosis workup.

Predicting Fracture Risk

• BMD measured by DXA scan is the most quantifiable fracture risk predictor for those who have not had a fragility fracture.
• Measures at the femoral neck are strong predictors of hip fracture risk.
• Relative risk of hip fracture is 2.5 for each decrease of 1 SD in bone density at the femoral neck.
• Relative risk of vertebral fracture is 1.9 for each decrease of 1 SD in bone density at the femoral neck.
• Osteopenia and osteoporosis are quantitative disorders of bone mineralization.
• Bone strength is determined by bone mineral density (BMD), and influenced by bone remodeling rates, bone size and geometry, microarchitecture, mineralization, damage accumulation, and matrix quality.
• The Fracture Risk Assessment Tool (FRAX) predicts an individual's 10-year fracture risk of sustaining a hip or other major osteoporotic fracture.
• FRAX is applicable to individuals aged 40 to 90 who have not received pharmacotherapy for osteoporosis.
• FRAX tool is available at http://www.shef.ac.uk/FRAX/ or https://www.fraxplus.org/calculation-tool/
• It combines clinical risk factors and femoral neck BMD T-score to calculate the 10-year fracture risk.
• The tool is useful for patients with osteopenia and high risk patients.
• FRAX algorithm can incorporate femoral neck BMD, or can input clinical risk factors to estimate clinical risk. Using clinical risk factors, a 65-year-old woman with no additional positive answers has a 9.3% 10-year risk for any osteoporotic fracture.
• FRAX tool for identifying osteoporosis (defined as T-score ≤ -2.5): Sensitivity 33.3%, specificity 86.4%, LR+ 2.4, LR- 0.77.

Osteoporosis Self-Assessment Tool (OST)

• Identifies individuals more likely to have low BMD.
• High risk for osteoporosis is indicated by a score of <2.
• OST Score = [weight (kg) – age (years)] x 0.2.
• For identifying osteoporosis (defined as T-score ≤ -2.5): Sensitivity 79.3%, specificity 70.1%, LR+ 2.4, LR- 0.29.

CAROC

• CAROC (Canadian Association of Radiologists and Osteoporosis Canada) uses bone density (femoral neck T-score) and age to predict 10-year fragility fracture risk.
• Corticosteroid therapy or a fragility fracture at a site other than hip or spine moves a patient to a higher-risk category.
• Two fragility fractures at a site other than hip or spine or fracture plus corticosteroid therapy places a patient in a high-risk category.
• Most Canadian DXA centres have been using CAROC in reporting BMD, though FRAX is now incorporated in most DXA software.
• FRAX has been shown to be slightly superior to CAROC as a predictor of fracture risk.

MORES

• MORES (Male Osteoporosis Risk Estimation Score) identifies men who are at risk for osteoporosis and need confirmatory DXA.
• Refer for DXA screening with a score of ≥ 6.
• MORES has a sensitivity of 93%.
• For 10-year prevention of hip fracture, number needed to screen is 279.

Osteoporosis Screening

• No studies have illustrated the effectiveness of osteoporosis screening to reduce osteoporotic fractures but many studies show that treatment can reduce fracture risk.
• Screening risks include misinterpretation of test results, increased patient anxiety, medication side effects, and cost.
• In women aged 60-64 (osteoporosis prevalence 6.5%), 435 individuals must be screened to prevent 1 vertebral fracture over 5 years, and 1000 must be screened to prevent 1 hip fracture.
• In women aged 65-69 (osteoporosis prevalence 12%), 233 individuals must be screened to prevent 1 vertebral fracture over 5 years, and 556 must be screened to prevent 1 hip fracture.
• In women aged 75–79 (osteoporosis prevalence 28%), 96 individuals must be screened to prevent 1 vertebral fracture over 5 years, and 238 must be screened to prevent 1 hip fracture.

Osteoporosis Screening Guidelines

• United States Preventative Task Force (2018): Screen for osteoporosis in women aged 65 years or older and in younger postmenopausal women at increased risk (>9.3% 10-year risk based on the FRAX calculator without BMD measurement, or high risk based on another tool such as the OST).
• USPTF has not established official screening recommendations for men.
• National Osteoporosis Foundation (2014): Screen for osteoporosis in women aged 65 years or older and men aged 70 years or older and in postmenopausal women and men aged 50-69 based on risk-factor profile and FRAX score. Screen for osteoporosis in postmenopausal women and men aged 50 years or older who have any adult fracture.

Osteopenia/Osteoporosis Additional Testing

• For moderate to severe osteopenia (T-scores between -1.5 and -2.4) or osteoporosis, consider lab tests to evaluate underlying causes.
• Testing includes blood urea nitrogen (BUN), creatinine, albumin, calcium, PTH (if serum calcium is abnormal), phosphate, alkaline phosphatase, complete blood count and 25-OH vitamin D.

Common Secondary Causes of Osteoporosis and Recommended Testing

• Primary hyperparathyroidism: Test for serum levels of parathyroid hormone, calcium, phosphorus, alkaline phosphatase.
• Secondary hyperparathyroidism from chronic renal failure: Perform renal function tests.
• Hyperthyroidism or excess thyroid hormone treatment: Perform thyroid function tests.
• Increased calcium excretion: Collect 24-hour urine to measure excretion of calcium and creatinine.
• Hypercortisolism, alcohol abuse, or metastatic cancer: Note history and when indicated appropriate laboratory studies.
• Osteomalacia: Test for serum levels of calcium, phosphorus, alkaline phosphatase, and 1,25-dihyroxyvitamin D.

Osteopenia/Osteoporosis Additional Testing - Diagnostic Imaging

• X-rays are used to detect fractures.
• If the X-ray shows evidence of osteopenia, confirm with a BMD measurement with a DXA scan.
• Bone scans can identify new fracture activity in patients with back pain and no obvious new fracture on X-ray.

Osteopenia/Osteoporosis Prevention and Treatment

• Interprofessional healthcare team with a focus on patient education is recommended.
• Lifestyle modifications: smoking cessation, alcohol abstinence or moderation (<2 drinks/day), caffeine moderation (<4 cups of coffee per day), ensure adequate protein, calcium, and vitamin D intake (calcium 1200-1500 mg daily, vitamin D 800-2000 IU daily), consistent physical activity (strength training, weight-bearing exercise, balance exercises), and fall prevention measures.
• Goals of therapy: prevent fractures, disability, and loss of independence and preserve or enhance bone mass.
• Osteoporosis Canada guidelines: Low 10-year fracture risk (<10%): re-assess risk in 5 years, moderate 10-year fracture risk (10-20%): repeat BMD testing in 1-3 years and reassess risk and high 10-year fracture risk (>20%): initiate pharmacotherapy.
• Pharmacologic treatment is universally accepted in patients diagnosed with osteoporosis (NNT = 10-20 patients) but is controversial in those with osteopenia (NNT > 100 patients).
• Bisphosphonates (alendronate, risedronate, zoledronate) are the most commonly prescribed medications. Alternatives include RANK ligand inhibitors (denosumab), selective estrogen receptor modulators (raloxifene), estrogen/progesterone hormone therapy, parathyroid hormone analogues (teriparatide), and calcitonin.
• Long-term bisphosphonate use has been linked to a rare risk of osteonecrosis of the jaw (associated with intravenous forms) and of atypical subtrochanteric femur fracture
• Discuss the harms and benefits of pharmacotherapy with a pharmacist or prescribing physician.

Osteoporosis-Related Fractures Prevention and Treatment

• Ensure timely patient follow-up after fragility fractures.
• Re-fracture risk is highest during the first 1-2 years after the initial fragility fracture.
• 50% of subsequent fractures occur within 3-5 years from the first event.
• Follow-up to determine FRAX score and complete DXA scan to establish the baseline BMD and T-score value.
• Consensus favors pharmacotherapy treatment in a patient with spine or hip fractures and a low BMD.
• The National Osteoporosis Society recommends starting treatment in all postmenopausal women with a history of any fragility fracture.
• The National Osteoporosis Foundation recommends performing DXA scans on patients sustaining nonvertebral fragility fractures.