Podcast
Questions and Answers
What is the primary role of parathyroid hormone (PTH) regarding calcium levels in the body?
What is the primary role of parathyroid hormone (PTH) regarding calcium levels in the body?
Which group has the highest prevalence of osteoporosis?
Which group has the highest prevalence of osteoporosis?
Which of the following methods is considered the gold standard for measuring bone mineral density (BMD)?
Which of the following methods is considered the gold standard for measuring bone mineral density (BMD)?
How is bone mineral density (BMD) typically expressed when comparing it to population norms?
How is bone mineral density (BMD) typically expressed when comparing it to population norms?
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What factor greatly increases the risk of fracture according to BMD measurements?
What factor greatly increases the risk of fracture according to BMD measurements?
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What is the expected outcome of combining high doses of PTH in terms of bone health?
What is the expected outcome of combining high doses of PTH in terms of bone health?
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Which condition can cause bone loss where resorption surpasses formation?
Which condition can cause bone loss where resorption surpasses formation?
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Which alternative site may be used to measure BMD if the recommended areas cannot be scanned?
Which alternative site may be used to measure BMD if the recommended areas cannot be scanned?
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Which T-score range indicates normal bone density?
Which T-score range indicates normal bone density?
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What is primarily affected in postmenopausal osteoporosis?
What is primarily affected in postmenopausal osteoporosis?
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Which of the following is NOT a risk factor for osteoporosis?
Which of the following is NOT a risk factor for osteoporosis?
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What indicates secondary osteoporosis?
What indicates secondary osteoporosis?
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Which factor contributes to the increased risk of falls in the elderly?
Which factor contributes to the increased risk of falls in the elderly?
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What is an essential consideration in differentiating primary from secondary osteoporosis?
What is an essential consideration in differentiating primary from secondary osteoporosis?
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Which of the following best describes the definition of osteoporosis according to the AACE 2020 guidelines?
Which of the following best describes the definition of osteoporosis according to the AACE 2020 guidelines?
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What role does estrogen deficiency play in osteoporosis?
What role does estrogen deficiency play in osteoporosis?
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Which scoring system is used to evaluate fracture risk over ten years?
Which scoring system is used to evaluate fracture risk over ten years?
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How is Z-score defined in relation to bone density data?
How is Z-score defined in relation to bone density data?
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What is a critical contraindication for starting Romosozumab (Evenity) therapy?
What is a critical contraindication for starting Romosozumab (Evenity) therapy?
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What is the initial management option for a postmenopausal woman with a BMD T-score of -3.0 and a history of vertebral fractures?
What is the initial management option for a postmenopausal woman with a BMD T-score of -3.0 and a history of vertebral fractures?
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Which of the following medications should be considered if a patient has osteonecrosis of the jaw history?
Which of the following medications should be considered if a patient has osteonecrosis of the jaw history?
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What is the recommended monthly dose of Romosozumab (Evenity) for treating osteoporosis?
What is the recommended monthly dose of Romosozumab (Evenity) for treating osteoporosis?
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What condition must be corrected before initiating therapy with Romosozumab?
What condition must be corrected before initiating therapy with Romosozumab?
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Which therapy is NOT recommended for a patient with an eGFR of 20 mL/min?
Which therapy is NOT recommended for a patient with an eGFR of 20 mL/min?
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Which serum vitamin D measurement is essential to optimize osteoporosis medication efficacy?
Which serum vitamin D measurement is essential to optimize osteoporosis medication efficacy?
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Which type of exercise is specifically known to improve muscle function and decrease falls?
Which type of exercise is specifically known to improve muscle function and decrease falls?
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What should be considered when taking calcium supplements?
What should be considered when taking calcium supplements?
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Which supplement is preferred to maintain serum 25(OH)D levels in adults over 50 years old?
Which supplement is preferred to maintain serum 25(OH)D levels in adults over 50 years old?
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What is a significant risk associated with taking fluoride salts for increasing bone mineral density?
What is a significant risk associated with taking fluoride salts for increasing bone mineral density?
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What is the primary function of thiazide diuretics in osteoporotic patients?
What is the primary function of thiazide diuretics in osteoporotic patients?
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Which pharmacological agent is specifically known to stimulate new bone formation?
Which pharmacological agent is specifically known to stimulate new bone formation?
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What is a significant contraindication for using calcium supplements?
What is a significant contraindication for using calcium supplements?
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Which of the following medications is primarily associated with inhibiting osteoclastic activity?
Which of the following medications is primarily associated with inhibiting osteoclastic activity?
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Which adverse effect is commonly associated with calcium supplements?
Which adverse effect is commonly associated with calcium supplements?
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What is the recommended dose of vitamin D for adults over 50 years to maintain optimal levels?
What is the recommended dose of vitamin D for adults over 50 years to maintain optimal levels?
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What is the primary purpose of prescribing estrogen or HRT according to the FDA guidelines?
What is the primary purpose of prescribing estrogen or HRT according to the FDA guidelines?
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Which of the following is an absolute contraindication for estrogen therapy?
Which of the following is an absolute contraindication for estrogen therapy?
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How does Raloxifene function in relation to bone health?
How does Raloxifene function in relation to bone health?
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What is a major adverse effect associated with Teriparatide (Forteo®)?
What is a major adverse effect associated with Teriparatide (Forteo®)?
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What should be monitored when a patient is prescribed Denosumab?
What should be monitored when a patient is prescribed Denosumab?
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Which statement correctly describes the use of Conjugated Estrogens and Bazedoxifene (Duavee®)?
Which statement correctly describes the use of Conjugated Estrogens and Bazedoxifene (Duavee®)?
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What is the maximum recommended duration of therapy for Teriparatide?
What is the maximum recommended duration of therapy for Teriparatide?
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What must be done at least 72 hours prior to procedures involving immobilization when using Raloxifene?
What must be done at least 72 hours prior to procedures involving immobilization when using Raloxifene?
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Which risk is specifically associated with the use of Denosumab upon discontinuation of therapy?
Which risk is specifically associated with the use of Denosumab upon discontinuation of therapy?
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What clinical symptoms are associated with the use of Abaloparatide (Tymlos)?
What clinical symptoms are associated with the use of Abaloparatide (Tymlos)?
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Study Notes
Osteoporosis
- Definition: Low bone mass, deterioration of bone tissue, disruption of bone architecture, compromised bone strength, increased risk of fracture
- Bone loss: Resorption > formation
- Morbidity, Mortality, Cost: Significant morbidity, mortality, and economic burden.
- Prevalence: Most prevalent in postmenopausal white women, with increasing incidence with age. Hispanics, men, and children also experience osteoporosis.
Bone Composition and Types
- Cortical (compact) bone: 80%, forms compact shell, highly calcified, surfaces of long and flat bones (forearm, hip) → structurally strong and protective.
- Trabecular (cancellous) bone: 20%, interior structure, high osteoclast and osteoblast turnover, common fracture sites (vertebrae, end of long bones, pelvis, wrist, ankle, ribs)
Bone Minerals and Matrix
- Minerals (50-70%): Hydroxyapatite (calcium and phosphorus)
- Organic matrix (20-40%), water (5-10%), lipids (<3%)
- Protein (in matrix): Provides elasticity and flexibility
Normal Bone Function
- Structural support: Skeleton provides structural support.
- Maintains homeostasis (Ca and other ions): Maintains calcium and ion homeostasis.
- Protects vital organs: Protects vital organs.
- Protects hematopoietic system (blood cell production): Protects the blood cell production system.
- Constant remodeling: In young adults, osteoblastic (formation) and osteoclastic (resorption) activity are equal (constant).
- Imbalance: Aging, medication, and certain diseases (e.g., menopause) cause an imbalance, resulting in bone loss.
Bone Remodeling
- Constant remodeling (resorption and formation): Bone is constantly being remodeled.
- Yearly remodeling: 28% trabecular and 4% cortical bone remodeled annually
- Time for resorption/formation: 3-4 weeks (resorption), 3-4 months (formation)
- Balance: Formation = Resorption = no bone loss.
- Bone loss: Formation < resorption (childhood and young adults)
- Osteoblasts and osteoclasts: Different cell types and functions.
- Normal aging: causes progressive decrease in osteoblasts and bone activity
RANKL
- Receptor activator of NF-κB ligand (RANKL): cytokine needed for osteoclast formation, function, and survival.
- RANKL bonds to RANK: fuses osteoclast precursors into multinucleated cells. Osteoclasts mature, attach to bone surfaces, and activate to resorb bone.
- Apoptosis prevention: Prevents apoptosis for osteoclast survival.
Bone Mineral Density (BMD)
- Reflection of balance: BMD reflects bone resorption and formation balance.
- Peak bone mass: Approaches peak in late teenage years (around 20-30).
- Growth and plateau: Peak bone mass achieved during growth, followed by a plateau period.
- Bone loss in women: Women lose 0.3-5%/yr cortical and 0.6-0.8% of cancellous bone after 3rd decade, significant loss after menopause.
- Loss in Men: Loss in 30's at slower rate.
Vitamin D
- Hormone regulation: Vitamin D and PTH maintain calcium homeostasis.
- Essential role: Plays essential role in calcium absorption.
- Conversion of Vitamin D: D3 & D2 from sun and diet to 1,25-dihydroxyvitamin D.
- Stimulation of bone: Stimulates bone matrix formation and bone maturation.
- Regulation: Levels of plasma Ca determine Ca balance.
- Intestinal absorption, renal tubular reabsorption, bone resorption: Released by PTH.
- Ca and P levels: 3 functions to maintain Ca levels to maintain free Ca in blood, stimulates bone resorption depending on Ca in blood
Vitamin D, PTH, Calcitonin, Phosphorus
- PTH and 1,25(OH)2D: Promote formation and resorption partially by increasing osteoblasts and osteoclasts. Excess PTH increases bone resorption.
- PTH and 1,25(OH)2D: Increase renal Ca retention, PTH promotes renal phosphate excretion.
- Calcitonin: Released with high Ca levels. Involved in intestinal calcium and phosphorus absorption, kidney excretion, and inhibiting bone breakdown.
Osteoporosis: Pathophysiology
- Low bone mass: Major cause is low bone mass and deterioration of bone tissue.
- Risk of fracture: Disruption of bone architecture, compromised bone strength increase the risk of fractures.
Radiologic and Ultrasound Quantification of Bone Loss
- BMD: Gold standard for measuring central skeletal BMD (hip and spine) by DEXA.
- Lower BMD → greater fracture risk.
- Z-Score: Number of SD from normal mean BMD value for patients of same age, sex, and ethnicity.
- Aid in diagnosis of secondary causes in children and premenopausal women.
- T-Score: Number of SD from normal mean peak BMD for young, healthy 25-30YO of same sex and ethnicity.
Risk Factors for Osteoporosis
- Lifestyle and habits: Weight, diet, smoking
- Genetic factors: Some genetic disorders predispose.
- Medications: corticosteroid use, certain antidepressants, anticonvulsants.
- Other medical conditions: Endocrine disorders, medical conditions, and illnesses increase risk.
Risk Factors for Falling
Environmental: Poor lighting, obstructive pathways, slippery surfaces, inefficient or lacking safety mechanisms in bathrooms
- Medical: Higher risks in older adults, individuals with certain medical backgrounds/conditions, certain medications (especially neuro-affecting medications etc)
- Neuromuscular: Affects balance and muscle strength
FRAX® and WHO
- FRAX®: Calculates 10-year probability of hip fracture and major osteoporotic fracture.
- WHO: Determines 10-year probability of hip fracture, along with clinical risk factors.
- Risk factors: Age, gender, family history of fractures, etc
BMD Testing: BHOF Guidelines
- WHO: Women ≥ 65 and men ≥ 70: Testing for low bone mass.
- Postmenopausal women 50-69 years old: Risk factor assessment.
- Postmenopausal women > 50 years who had adult age fractures: Testing.
- Facility quality assurance measures
- Same facility/densitometry device preference for consistent data.
BMD Testing: Guidelines
- DEXA: Standard for measuring hip and spine BMD
- Forearm (distal third of radius): Alternative if areas cannot be scanned
- WHO: Hip BMD best predictor of hip fractures
- US Preventative Service Task Force: Hip and spine (lumbar)
- AACE: Lumbar spine, femoral neck, total hip
- Bone Foundation: Lumbar Spine, hip
- AACE: Lumbar spine, femoral neck, and total hip (one-third radius if needed)
- Heel/finger scans, used in pharmacy and clinics. Helpful for screening tool.
Bone Density Data
- Z score: number of SD (standard deviations) from normal mean BMD value for patients of same age, sex, ethnicity. Used to diagnose osteoporosis (in secondary causes) for children, and premenopausal women.
- T score: number of SDs from normal mean peak BMD for young, healthy adults (25-30YO) of same sex and ethnicity. Used to classify BMD for osteoporosis diagnosis
Categories/Pathophysiology
- Postmenopausal osteoporosis: Most prevalent, affects trabecular bone, Vertebral and distal forearm fractures
- Age-related: Bone loss with age, Affects trabecular and cortical bone. Risk for vertebral, hip, and wrist fractures increases
- Secondary: Due to medication, smoking, alcohol, or medical conditions (e.g., chronic liver disease, hypogonadism) Affects trabecular and cortical bone, multiple low-trauma fractures (esp. young age) is concerning.
Lifestyle Risk Factors
- Low calcium intake.
- High caffeine (↑ Ca excretion).
- Cola/Beverage and phosphoric acid.
- High salt and Vitamin A intake.
- Alcohol use: ↑ falls, poor nutrition
- Smoking (active or passive)
- Inadequate physical activity
- Falling
- Aluminum antacids
- Thinness (< 127lb or BMI < 21/kg/m²)
- Genetic
- Endocrine
- Hematological
- Miscellaneous
Exercise
- Improves muscle function, balance
- Aerobic: Improves cardiovascular health
- Weight-bearing: Works against gravity, improves muscle function.
- Benefits: ↓ falls, ↑ balance, ↑ muscle strength/mass, ↑ coordination, posture, range of motion, endurance, flexibility, agility, and ↓ bone loss
- Long-term: ↑ peak BMD
- WB (weight-bearing): Walking, running
- MS (muscle strengthening): Weight training
Thiazide Diuretics
- Example: Hydrochlorothiazide
- ↑ urinary Ca reabsorption → ↑ Ca retention
- Cannot be prescribed solely for osteoporosis
- Use supplemental calcium if taking glucocorticoids (excreted > 300mg Ca in 24hr)
Fluoride Salts
- ↑ BMD at spine, but not as strong as normal bone, no hip protection
- May cause osteomalacia-like bone defect and loss of cortical bone as it increases trabecular bone.
- May ↑ nonvertebral fracture at high doses.
- No fluoride products approved for prevention or treatment of osteoporosis.
- Do not use. Concurrently, adequate calcium/supplemental calcium intake. Administer calcium correctly.
Pharmacological Agents
- Antiresorptive drugs: Inhibit osteoclastic bone resorption (e.g., bisphosphonates, raloxifene, calcitonin, estrogen, denosumab)
- Anabolic agents: Stimulate bone formation (e.g., teriparatide, abaloparatide)
Calcium Supplements
- Calcium: Delays BMD loss and ↓ fractures when combined with vitamin D.
- Dietary sources: Dairy, Dark Leafy Greens (absorption affected by oxalic acid).
- Supplements: Divided doses (> 500-600mg/day) with sufficient time interval between doses
- Absorption: improved by taking with meals low in fiber.
Vitamin D
- Needed for calcium absorption in the GI tract and affects bone resorption
- Improves muscle strength and balance
- Dietary sources: Vitamin-D fortified milk, cereals, egg yolks, salt-water fish, liver, green vegetables, bread
- Exposure: 5-15 minutes daily sunlight between 10 am and 3 pm is often sufficient.
- Sunscreen: ↓ vitamin D absorption by ≥97.5% when using SPF ≥8
- Calcitriol (active form of vitamin D): preferred.
Bisphosphonates
- Alendronate (FosamaxⓇ): 10mg/day or 70mg once weekly.
- Risedronate (ActonelⓇ): 5mg/day or 35mg once weekly. One 150mg dose monthly
- Ibandronate (BonivaⓇ): 150mg monthly
- Zoledronic acid (ReclastⓇ): 5mg yearly IV and 400mg QD for 14 days followed by 500mg calcium QD for 76 days.
- Adverse effects: Maximum suppression → 3 months after initiation of therapy, esophageal ulcer, esophageal stricture, dyspepsia, dysphagia, acid regurgitation, nausea/diarrhea, arthralgia...
Calcitonin
- Peptide normally produced from C cells of thyroid, inhibits osteoclasts and ↓ bone resorption
- Nasal formulation (less adverse effects)
- Indication: Treatment for osteoporosis in women ≥ 5 years postmenopausal
- Dose: 200IU daily (alternate nostrils daily)
- Increased BMD and decreases vertebral fractures
- FDA panel 2013: Discontinued in women
Estrogen and Hormone Replacement Therapy (HRT)
- Approved for prevention of osteoporosis
- Stabilizes bone remodeling, ↑ Ca absorption, promotes calcitonin synthesis
- ↑ number of vitamin D receptors on osteoblasts, and influences osteoblasts and osteoclasts
- ↑ BMD, ↓ vertebral and hip fractures
- ↓ LDL, ↑ HDL, ↓ triglycerides
- Relieves hot flashes, sweating, arthralgia, myalgia
- Increased BMD compared to calcitonin and raloxifene, but less than bisphosphonates, denosumab, teriparatide
- Disadvantages: ↑ risk of endometrial hyperplasia, endometrial cancer (if uterus intact), and breast cancer; weight gain, fluid retention, vaginal bleeding, breast enlargement and tenderness ↑ risk of thrombosis
Raloxifene (Evista®)
- Estrogen agonist/antagonist
- Approved for prevention and treatment of osteoporosis
- Estrogen agonist on bone, blood clotting, and lipid metabolism
- Estrogen antagonist on endometrial and breast tissue
- Reduces bone resorption, ↑ BMD and ↓ vertebral fractures
- Does not stimulate endometrium and does not cause endometrial hyperplasia
- ↓ LDL, ↑ HDL
- Adverse effects: Hot flashes, venous thromboembolism, peripheral edema, leg cramps
- Contraindications: Active or past history of cardiovascular or pulmonary thromboembolic events (DVT, stroke, MI, and pulmonary embolism).
Conjugated Estrogens and Bazedoxifene (DuaveeⓇ)
- Combination of conjugated estrogens with estrogen agonist/antagonist.
- Prevention of postmenopausal osteoporosis in women with a uterus.
- Contraindications: Undiagnosed abnormal uterine bleeding, known, suspected, or past history of breast cancer, known or suspected estrogen-dependent neoplasia, active or past history of venous thromboembolism. Active or past history of arterial thromboembolism, hepatic impairment or disease, protein C or protein S deficiency or other thrombophilic disorders, and pregnancy or nursing mothers, use not recommended for age > 75 or renal impairment.
- Should not take additional estrogens or other estrogen agonist/antagonists
Teriparatide (Forteo®)
- Biologically active N-terminal region (1-34) of human PTH
- Stimulates bone formation, bone remodeling rates, and osteoblast number/activity
- Treatment for postmenopausal women with osteoporosis at high risk for fracture
- Treatment for men and women with glucocorticoid-induced osteoporosis at high risk for fracture
- Continuous exposure to elevated PTH levels results in osteoclast bone resorption, while intermittently administered PTH stimulates formation
- Increases trabecular bone (lumbar spine and femoral neck) more than cortical bone (distal radius)
- Considerations: Administration of PTH intermittently stimulates bone formation > resorption, ↑ BMD, ↓ risk of vertebral and nonvertebral fractures
- Precautions: Increased risk of osteosarcoma, hypotension/orthostatic hypotension, Nausea, dizziness, leg cramps, transient ↑ serum Ca, ↑ urinary Ca excretion, arthralgia, kidney stones, pain at injection site.
- Contraindications: Open epiphyses, metabolic bone diseases, bone metastases, skeletal malignancies, history of prior external beam radiation therapy of skeleton, hereditary disorders etc
- Precautions for use: Preexisting urolithiasis, hypotension, pregnancy, severe renal insufficiency, digoxin therapy, and concurrent high-risk medications.
Abaloparatide (Tymlos®)
- Human parathyroid hormone-related peptide(1-34) analog
- Treatment of postmenopausal women with osteoporosis and high fracture risk.
- Treatment for increase bone density in men with osteoporosis (high fracture risk).
- Dose: 80 mcg subcutaneously once daily (peri-umbilical region)
- Potential adverse effects include orthostatic hypotension (initial sit or lie down), hypercalcemia, hypercalciuria, urolithiasis, headache, fatigue, upper abdominal pain.
Denosumab (Prolia®)
- RANK ligand (RANKL) inhibitor.
- Fully human monoclonal antibody against receptor activator of nuclear factor-KB ligand (RANKL).
- Binds to RANKL from stimulating RANK receptor on osteoclasts' surface and prevents osteoclast formation, function, and survival then reduces bone resorption, and enhances cortical and trabecular bone mass + strength
- Treatment of postmenopausal women with osteoporosis at high risk for fractures
- Treatment for increase bone mass in men at high risk for fractures receiving androgen deprivation therapy/adjuvant aromatase inhibitors
- Treatment of glucocorticoid-induced osteoporosis (men and women).
- Contraindications: Hypocalcemia
- Precautions: Pre-existing urolithiasis, hypotension, pregnancy, severe renal insufficiency, digoxin therapy
Romosozumab (Evenity®)
- Sclerostin inhibitor → protein in osteocytes that inhibits bone formation.
- Treatment of postmenopausal women with osteoporosis (high fracture risk).
- Dose: 210mg subcutaneously (2 separate injections required, one after another, every month for 12 months).
- Should be administered by a healthcare provider
- Contraindications: Hypocalcemia before initiating therapy, and hypersensitivity to the medication; not for open epiphysis, etc
- Precautions: Monitor for orthostatic hypotension, arthralgia, headache, hypocalcemia, osteonecrosis of the jaw, atypical femur fractures, cardiac events, and other adverse reactions
Glucocorticoid-Induced Osteoporosis
- ↓ bone formation by inhibiting osteoblast formation; ↑ bone resorption by ↑ Ca excretion, ↓ Ca absorption, ↑ stimuli osteoclasts.
- Largest bone loss: Occurs within the first 6 months and then slows
- Associated with all glucocorticoid doses and formulations.
- Treat with lowest dose possible for shortest time. High daily doses cause greater risk at high doses and duration.
- Calcium and vitamin D supplements as appropriate recommendations.
- Bisphosphonates, teriparatide, and denosumab are indicated.
Paget's Disease
- Bone remodeling: Excessive resorption of osteoclasts → increase or excessive in bone formation (dense, disorganized, not effective mineralized bone matrix leading to weaker bone).
- Altered bone architecture → more prone to fractures or deformity.
- 3 Phases: ↑ osteoclasts, ↑ bone resorption, osteoblasts then bone resorption.
- Affects pelvic bones, femur, lumbar spine, thoracic spine and skull.
- Symptoms: Asymptomatic in most cases, bone pain, increased head size, bowing of limbs, curvature of the spine (kyphosis), hip pain, cartilage damage...
Osteomalacia
- Bone mineralization: Deficient in calcium and/or vitamin D.
- ↓ bone mineralization causes skeletal deformities (e.g., rickets in children, osteomalacia in adults).
- Causes: Deficient vitamin D, malabsorption, sunscreen use, dark skin pigmentation. Medications such as anticonvulsants, al antacids and other factors.
- Consequences: "Soft bones".
- Treatment: Depends on cause. Vitamin D and calcium are crucial. Bisphosphonates, teriparatide and other osteoporosis medications are contraindicated.
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Description
Test your knowledge on osteoporosis, its risk factors, and bone mineral density measurements. This quiz covers important concepts related to parathyroid hormone and how it influences calcium levels in the body. Understand the implications of bone health and the methods used to assess it effectively.
