Osteoporosis: Diagnosis, Prevention, and Treatment

• Osteoporosis is a significant health condition that can be managed with proper intervention.

Objectives

• Diagnose osteopenia and osteoporosis correctly.
• Understand the pathogenesis of osteoporosis.
• Identify common secondary causes of bone loss to address underlying issues.
• Use FRAX to predict osteoporotic fracture risk.
• Learn strategies for prevention and treatment.

Topics Covered

• Osteoporosis Definition
• Epidemiology and Impact
• Bone Remodeling and Bone Loss in Aging
• Risk Factors for Osteoporosis
• Prediction and Diagnosis of Fractures
• Prevention and Treatment
• Vertebral Fracture Management

Definitions of Bone Loss Disorders (1 of 2)

• Osteoporosis is diagnosed when a bone mineral density (BMD) measurement at any site is ≤ 2.5 standard deviations below the young-adult standard, with or without a previous fracture.
• A T-score less than -2.5 indicates osteoporosis.
• Primary Osteoporosis is age-related.
• Secondary Osteoporosis results from other diseases or medications.
• Osteoporosis can be clinically diagnosed in those at-risk who sustain a fragility or low-trauma fracture.

Definitions of Bone Loss Disorders (2 of 2)

• Osteopenia is characterized by low bone mass.
• T-score is less than -1 but greater than or equal to -2.5

Epidemiology of Osteoporosis

• Osteoporosis impacts people across all ethnic backgrounds.
• The annual osteoporotic fractures in the US are 2 million.
• 1 in 2 postmenopausal women and 1 in 5 men >50 years old will have a fracture in their lifetime.
• This condition lowers quality of life, function, and independence.
• There is increased morbidity & mortality, with 20% excess mortality in the year after a hip fracture, with the rate of death in men nearly double that of women.

Bone Remodeling

• Bone actively repairs itself via remodeling
  • Bone resorption (via osteoclasts)
  • Bone formation (via osteoblasts).
• The remodeling cycle becomes unbalanced after menopause and with aging in men & women.
  • Bone resorption increases more than bone formation, resulting in net bone loss.
• Bone loss leads to osteopenia, osteoporosis, and fractures.

Lifetime Changes in Bone Mass

• Bone mass increases rapidly from puberty to mid-20s and 30s, reaching peak bone mass.
• From mid-30s to 40s, stability for a few years, then slow bone loss with the rate dependent on risk factors.
• Women experience menopause from mid-40s to 50s, which causes rapid bone loss of ≥ 7% per year for ≥7 years.
• Both men and women continue bone loss of 1%-2% per year from mid-50s to late life.
• Men experience rapid cortical bone loss ≥7% per year for ≥7 years from mid-70s to late life.
• Risk factors include: low calcium intake, smoking, alcoholism, certain drugs, physical activity, nutrition, endocrine status, and comorbid diseases.

Risk Factors for Osteoporosis (1 of 7)

• Osteoporosis risk factors can be intrinsic, or genetic.
• Intrinsic factors include multiple factors on peak bone mass, rate of bone resorption, and rate of bone formation.
• Genetics can also be a contributing factor, heritable traits account for 75%-80% of a person's peak bone mass.
• Other diseases, such as diabetes, are heritable and associated with higher risk of osteoporosis.
• The determination of sex hormone traits and sensitivity to hormonal factors is also genetic.

Risk Factors for Osteoporosis (2 of 7)

• Sex hormone imbalance, specifically estrogen deficiency, leads to bone loss.
• Increased resorption
• Increased osteoclast activity
• Fracture risk is inversely related to estrogen levels in postmenopausal women.

Risk Factors for Osteoporosis (3 of 7)

• Sex hormone imbalances negatively affect osteoporosis, androgens are important determinants of peak bone mass in young men and falls gradually as men age
• An increase in sex hormone binging globulin can lead to decrease in bioavailable testosterone
• Severe male hypogonadism can cause osteoporosis
• The effect of moderate decreases in testosterone levels in aging men on rate of bone loss is uncertain
• Estradiol in older men has been positively associeted with bone mineral density

Risk Factors for Osteoporosis (4 of 7)

• Weight-bearing bones require a level of stress from gravity while walking and dynamic strain of muscular contractions maintain normal bone mass density(BMD)
• Exercise that stresses or mechanically loads bones reduce BMD loss in the spine and hip for postmenopausal women
• Examples of exercise that improve BMD are strength training, aerobics, Tai Chi, Walking

Risk Factors for Osteoporosis (5 of 7)

• There is a higher probability of Calcium and vitamin D insufficency
• Aging skin & sunlight exposure and conversion of 7-dehydrocholesterol to vitamin D3 by ultraviolet light leads to vitamin D insufficiency
• Vitamin D insufficiency Calcium absorption is decreased
• Older black Americans are at particular risk of vitamin D deficiency as they age.
• Impaired intestinal absorption of calcium may occur as a result of disease or aging.

Risk Factors for Osteoporosis (6 of 7)

• Vitamin D deficiency contributes to increased bone loss, promotes muscle weakness that can increase the risk of falls, and leads to secondary hyperparathyroidism.
• In order to maintain normal serum levels of calcium PTH increases.
• When PTH becomes chronically elevated PTH acts as a stimulator of bone resportion by stimulating osteoclasts
• Trials show that supplementation of both Vitamin D and Calcium can reverse secondary hyperparathyroidism (SOE=A); increase bone mass (SOE=B); decrease bone resorption (SOE=A), fracture rates (SOE=B), and possibly the frequency of falling (SOE=C)

Risk Factors for Osteoporosis (7 of 7)

• Extrinsic factors that effect the development of Osteoporsis include smoking
• Smoking : Increases risk of fractures by both current and former smokers, however it is more impacted by the amount of nicotine smoked and how recently one quit smoking than by the duration of tobacco use
• High Alcohol intake is risk factor, drinking >3 oz of alcohol per day early and/or later in life increase bone loss and fracture risk

Diagnosis and Prediction of Fracture

• Osteoporosis is a preventable disease; however, it is often not diagnosed until a fracture occurs.
• The National Osteoporosis Foundation recommends clinical assessment of osteoporosis risk factors for all postmenopausal women and men ≥50 years old.
• The diagnosis of osteoporosis should be considered in any older adult with a fracture.
• BMD measurement is used to establish the diagnosis of osteoporosis in those at high risk clinically but without a prior fragility fracture.

Additional Risk Factors for Osteoporosis

• Age, postmenopausal in women and >70 yrs in men
• Female sex
• Low body weight (BMI <20)
• 10% decline in weight (from usual adult body weight)
• Physical inactivity
• Glucocorticoids
• Previous fragility fracture as adult
• Current smoking
• Low dietary calcium
• White or Asian race
• Alcohol intake ≥ 3 drinks/day

Modifying Risk of Osteoporosis (1 of 2)

• Encourge regular, weight-bearing exercise at least 5 times per week for 30 minutes, eat nutriciously, and intake adequate calcium supplementation(1200 mg/day in divided doses) and vitamin D3(800-1000 IU/day)
• Encourage smoking cessation, avoid excessive alcohol consumption

Modifying Risk of Osteoporosis (2 of 2)

• Certain medications can increase the risk of osteoporosis
• Glucocorticoids
• Anticonvulsants
• Long-term heparin
• Excess thyroid hormone replacement
• Methotrexate -Calcineurin Inhibitors -PPIs -GnRH agonists used for prostate cancer -Aromatase inhibitors used for breast cancer -Cancer Chemotherapeutic agents -SSRIs -Antiretrovirals

Common Secondary Causes of Osteoporosis

• Male hypogonadism
• Vitamin D insufficiency
• Idiopathic hypercalciuria
• Malabsorption (often celiac disease)
• Multiple myeloma
• Glucocorticoids
• Primary hyperparathyroidism
• Solid organ transplantation

Recommended Initial Laboratory Testing in Those with Osteoporosis

• Fasting comprehensive metabolic panel (including albumin and alkaline phosphatase.) Serum phosphorus and 25(OH)D concentration must be examined.
• Check Serum parathyroid hormone & Thyrotropin (TSH or thyroid-stimulating hormone)
• Perform a 24-hour urine collection to observe the amount of calcium and creatinine
• Run a Complete Blood Count (CBC) and Serum testosterone

Clinical Evaluation (1 of 2)

• Take a thorough history to uncover risk factors that lead to bone fragility, and to understand the setting in which fracture occurred.
• The physical exam should assess for signs of fracture as well as secondary causes.

Clinical Evaluation (2 of 2)

• Tests must be completed to measure vitamin D level, and bone density
• Biochemical markers are controversial

Bone Density Measurement (1 of 3)

• The best predictor of fracture risk is bone density measurement. -There is 10x greater risk in women in the lowest quartile than in the highest
• Performing Dual-energy x-ray absorptiometry (DEXA) measure bone and muscle tissue -Can measure the Anterior-posterior spine, lateral spine,calcaneus and wrist. Most accurate when completed at central (proximal femur and lumbar spine)

Bone Density Measurement (2 of 3)

• USPSTF Testing Recommendations:

65 for women regardless of risk-factor status <65 if 10-year factor is equal-greater to that of a 65-year old white women with out additional risk factors

• NOF (recommends): Screening men that are => 70 even without risk factors There in insufficient evidence to determine the need for screening in men

Bone Density Measurement (3 of 3)

• Several factors are important when examining BMD of the spine over time
• L1-4 of lumbar vertebrae should be measured when deciding on therapy
• Proximal Neck is preferred over Femoral neck because fractures will result if anything becomes loose
• It is critical to scan patient on the exact same DEXA machine because unaccountable machine differences can damage a patients results.

FRAX

• Algorithm of clinical and BMD information to model the 10- year fracture probablity in men and women
• Free online too located from a source to allow for Osteoporosis risk assessment
• Valid cases : Patients cannot be over 90/under 40, or currently on treatment. Does not give fracture risk in patients with good Femoral neck results, and normal spinal results (spinal stenosis)
• Limited Data to only White, Black, Asian and Hispanic population.

Vertebral Fracture Assesment

• Vertebral fractures are highly associated with a future increase of risks and mortality.
• Can be present in patients with T scores -2.5 or greater, and it is used as a tool for BMD testing.

Limitations on the Use of Biochemical Markers

• Not recommended for routine exams, and has substantial overlap that inhibits the data quality of the study.
• Cannot compare markers.
• Not fully complete

Biochemical Markers of Bone Turnover

• Bone resorption markers:
• Deoxypyridinoline crosslinks of type I collagen
• And Cross linked N telopeptides of type I collagen
• Bone formation maker
• Bone alkaline phosphate

Whom To Treat

• Postmenopausal women &men over the age of 50 with an abnormal bone density
• National Foundation recommends treatment with FRAX US algorithim

Treatment Considerations

• Tretment should be considered in any patient with > 1-year life expectancy
• No clear guidlines for when to start medication /pharmacologic treatment for fragility fracture. General concensus is start treatment about 2 weeks after fracture.
• Decisons should incorporate patient preferances, risk levels, benefits, harm and costs.

Preventing and Treating Osteoporosis

• Exercise, adequate daily intake and pharmacologic options: -Bisphosphonates
• Selective Estrogen Receptor Modulators
• Calcitonin -Estrogen replacement -Parathyroid hormone RANLK inhibitors -Investigational agents

Exercise

• Bone mass decreases during reduced physical activity or immobilization.
• Weight-bearing exercise such as walking is recommended for all adults.
• Start slowly and gradually increase days and time spent walking.
• Regular exercise is positively associated with BMD, and starting later in life can help preserve BMD.

Calcium and Vitamin D (1 of 3)

• Calcium recommended requirements:
• POstmenapausal and Men +70 yr and over require 1200 per day
• Men 51-70 need 1000
• Most should require daily intake dairy to supplemt to insure adequate supplementation since post men women already average about 500-700 mg/Day
• Do not exceed a max of 2000mg.

Calcium and Vitamin D (2 of 3)

• The average Vit D levels = 600 IU daily
• For all Men and Women 50+ average 800 UI daily There are a variet of supplementation method, and all over 4000 IU is considere unsafe, and supplement is required to acheieve a serum 25(OH) D concentrations of 30mg
• Too little intake is less the < 400Ui

Calcium and Vitamin D (3 of 3)

• Monitoring of Vit D levels, in theory, are needed to meet desired goal but Vitamin D insufficiency has been defined to be between 21-29 ng/ml and under 20mg/ml signifies Vit D deficiency.
• American Geriatrics Society stated the desired level in serum is 30mg

Bisphosphonates (1 of 2)

• Approved for osteoporosis prevention in postmenopausal women and for treatment in men and women
• Increases BMD and decreases fractures at the spine and hip in postmenopausal women
• Decreases vertebral fracture rate, and has a low absolute vertebral fracture rate when treating Glucocorticoids

Bisphosphonates ( 2 of 2)

• Can be given Weekly(alendronate+ risedronate), Monthly ( risdeonate + ibandronate)
• treatment duration depends on person and ambulation ability

Bisphosphonates: Side Effects

-GI: abdominal pain, diarrhea, nausea

• Musculoskeletal: osteonecrosis and atypical fractures (both rare in patients being treated for osteoporosis)
• Acute Phase: myalgias + headaches after taking
• Atypical fracture of fmeur in people using it for 5+ years.

Bisphosphonates Compared (1 of 2)

• Alendronate has 70mg available + Risedronate with 35 mg; can be used with people for prevention for osteoporosis
• Special considertions:Bisphosphonates should NOT exceed a CrCl
• 7% risk reduction

Bisphosphonates Compared (2 of 2)

• Ibandronate at 150MG and Zoledronic with 5mg for treatment can be used but patients must be adherant to dose

Bisphosphonates Instructions

• Take drug first thing in the morning without other medications, in an upright position with minimal 8oz tap water

Monitoring Bisphosphonates Therapy

• Advise medical providers if a patient reports groin or thigh pain.
• Rare to have acute phase but to counter act it report these to physicians
• Low absolute risk 1:10,000

Discontinuation of Bisphosphonate Therapy

• Uncertain; some studies suggest 1 -2 year brake due to the benefits outweighing fracture risks.
• FLEX suggests Alendronate has 5 years of effects, regardless: "drug holiday" of 1-2 Some opinionated suggestions suggest bisphosphonates should be cancelled under people with > 2 year life expectency

Selective Estrogen Receptor Modulators (SERMs)

• Acts a receptor for bones and heart.
• Estrogen antagonist within breast/uterine tissue.

SERMs Raloxifene

• Treats and prevent post men women.
• 60mg Day, and compared to the use of a Placbo + reduced vertebral fractures
• 24 reduced relative risk of breast cancer
• increased bone density
• Increased venous thromboembolism and stokes
• Symptoms of flulike syndrom plus edema and pain
• Can be used to treat breast cancer prevention

Calcitonin (1 of 2)

• Inhibitor for bone resportion + decreases veterbral fractures
• No Hip, Nonvertebral fractures are noted May provide analgesic effects on women with bone comphresion fractures - FDA says not to due to increased breast cancer.

Calcitonin 2 of 2

• Subcutaneous and injections, for treatment of Hypocalcemia, and is suggested for vomiting nauseas with possible increased risk of cancer
• Can be taken 3-5 times a week

Estrogen Replacement

• prevents bone loss at the hip if the treatment starts ten years within being in menapause + prevents osteoporosis.
• should not be a 1st line method/treatment - risk of bone cancer if using in the heatlh inititive + increased threat of strok/enous.

Parathyroid Hormone

• Will increase bone levels with resportion + BMD on people with severe fractures
• Black box warning: patients with a history of skeletal irritation.

Denosumab

• Denosumab reduces bone turnover when taken (60mg for injection every 6 months) and if there is a side effect then consult MD. For post men women, who have failed bone re enforcement therapies, it is a solid alternative

Strontium Ranelate

• Anabolic agent + increases bone.

Investigational Agents

• Anti-Sclerostin= increases bone formation, not FDA appproved
• Can have adverse side effects related to cardia events

Monitoring

• Checking the history of serial BMD on therapy with 2 year intervals can reveal signs of: failure (to maintain bone density)-Non Adherance: Failure
• Confirm poor compliance is a indication for risks of fracture

Vertebral Compression Fractures

_ Majority = Asymptomatic - with a kyposis

• Aching during Spinal +radiographs and Kyposis
• Typically 2 +4 weeks

Managing Vertebral Fractures (1 of 2)

• Treatment of vertebrals are pain control (NSAIDS, narcotics, Calicitonin), PT And spinal stability

Managing Vertebral Fractures (2 of 2)

• Education is key for Vertebral Fracture and Kyphoplasty is a optional treatment and should only be used if the patient understands the risks and benefits.

Choosing Wisely Recommendations:

• Do no routinely repeat BMDs more then every 2 years + Do not Vitamin D population based screening

Summary (1 of 2)

• High personal / finacial cost = Osteoprosis can be preventied with a strong risk of treatment, suplementing calcium and Vitamin D intake.
• Osteoprenia with DXA and Osteoprosis may reduce bone loss

Summary (2 of 2)

• Osteporosis prevention &treatment combine : Risk reduction & Vit d intake. Medication and Pharmaceitial Therapies depend on person Pain related ostperortics needs NSAIDs Calcitonin and physical treatment