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Questions and Answers
What are the major functions of bone?
Structural support, protection of organs, marrow development and storage, mineral storage
Which type of bone tissue is known as the hard outer layer?
Osteoporosis is characterized by increased bone strength and improvement of bone quality.
False
A fracture occurring spontaneously or following minor trauma such as a fall from standing height or less is known as a ______________ fracture.
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What is the first-line pharmacotherapy for most cases?
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Monitoring of therapy should include regularly assessing adherence, tolerability, and new risk factors.
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What tool or tools are mentioned for risk assessment in osteoporosis?
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Denosumab requires uninterrupted long-term commitment to treatment and transition to anti-resorptive agent if __________.
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What is the abbreviation for Atypical Femur Fracture?
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Which of the following is a side effect of Denosumab?
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______ is suggested as a treatment for females who have contraindications or substantial intolerance to, or who choose not to take, other suggested therapies, should be used only in those who are not at high risk of VTE.
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Match the pharmacotherapy options with their corresponding activities: Bisphosphonates, Anabolic Therapy, Denosumab, Raloxifene
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Bone Mineral Density (BMD) may be repeated at a shorter interval only if there are new fractures.
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What type of exercise can improve Balance and Functional Training?
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What is the recommended daily intake of Calcium for men above 70 years old?
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What is the recommended daily intake of Vitamin D for adults above 50 years old?
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What type of exercises can improve physical functioning or Quality of Life (QoL)?
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What is the upper limit of Vitamin D intake recommended by Health Canada?
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Which type of exercise can react to things that upset one's balance?
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What is the primary goal of exercise in fall and fracture prevention?
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Which muscle group is targeted in exercises that reduce the base of support?
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What is the recommended approach to nutrition in osteoporosis management?
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What is the minimum daily dose of vitamin D recommended in pharmacotherapy trials?
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Which of the following is a risk factor for osteoporosis?
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What is the mechanism of action of bisphosphonates in osteoporosis management?
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What is a potential complication of long-term bisphosphonate use?
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Why may denosumab be preferred over bisphosphonates in some cases?
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What is a key consideration when recommending calcium supplementation for osteoporosis?
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Which of the following is a benefit of pharmacotherapy in osteoporosis?
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What is an important consideration when assessing osteoporosis risk factors?
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What is the recommended duration of initial treatment with bisphosphonates?
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What is the recommended frequency for reassessing BMD and fracture risk in osteoporosis?
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What is the primary indication for denosumab in osteoporosis?
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What is the recommended approach to monitoring therapy in osteoporosis?
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What is the recommended duration of initial treatment with bisphosphonates for individuals with a history of hip, vertebral, or multiple non-vertebral fractures?
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Why is it important to not delay denosumab injections by more than 1 month?
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What is the recommended duration of treatment with teriparatide?
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What should be used to determine a patient's risk for fractures?
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When should BMD be repeated at a shorter interval?
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What should be assessed after 3 years of stopping bisphosphonate therapy?
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What is the recommended duration of treatment with romosozumab?
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What should be done if there is an inadequate response or ongoing substantial concerns for fracture on bisphosphonate therapy?
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What should be considered when deciding on anabolic therapy?
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Study Notes
Bone Functions
- Provides structural support
- Protects organs
- Supports marrow development and storage of blood cells
- Stores minerals (Ca, Mg, PO4)
Bone Composition
- Osteoid (non-mineral, organic part of bone matrix): made of collagen and non-collagenous proteins
- Minerals (hydroxyapatite, Ca, and PO4): provides stiffness and strength
- Osteoblasts (bone forming cells): synthesize and secrete organic matrix, regulate mineralization
- Osteocytes and lining cells: communicate with bone cells, formerly osteoblasts that become incorporated into bone matrix or cover the surface as lining cells
- Osteoclasts (bone resorbing cells): adhere to bone, remove it by acidification and proteolytic digestion
Bone Remodeling
- Resorption and formation: osteoclasts remove bone, osteoblasts synthesize new bone matrix
- Osteoclast cell signaling:
- RANKL (Receptor activator of nuclear factor kappa β ligand): stimulates progenitor cell differentiation to osteoclast
- Estrogen: inhibits RANKL release, stimulates osteoclast apoptosis
- Calcitonin: inhibits RANKL release, decreases osteoclast bone resorption
- Osteoblast cell signaling:
- Parathyroid hormone (PTH) and Parathyroid-related protein (PTHrP): stimulate osteoblast differentiation and activity
- Osteoprotegerin (OPG): binds to RANKL, stopping bone resorption
Calcium Homeostasis
- Calcium absorption: usually 30-35%, decreased with low vitamin D (10-15%)
- PTH release: stimulated by low calcium, increases osteoclast bone resorption
- Calcitonin: inhibits RANKL release, decreases osteoclast bone resorption
Osteoporosis
- Reduced bone strength and deterioration of bone tissue, increasing risk of fractures
- Most common fractures: hip, spine, wrist, and shoulder
- WHO definition: bone density < 2.5 SD below the mean for young healthy adults of the same sex (T-score of -2.5)
Clinical Assessment for Osteoporosis
- Identify risk factors
- Assess for signs of undiagnosed vertebral fracture(s)
- Risk factors:
- Previous fracture after age 40
- Glucocorticoids (> 3 months in the last year; prednisone dose ≥ 5 mg daily)
- Secondary osteoporosis
- Parent fractured hip
- Current smoking
- Alcohol ≥ 3 drinks/day
- Body Mass Index < 20 kg/m²
- Recommended dietary intake:
- Calcium-rich foods (milk products, fortified beverages, canned salmon)
- Vitamin D-rich foods (fatty fish, fortified foods, eggs)
- Protein-rich foods (beef, pork, chicken, fish, eggs, milk products, legumes, beans, nuts, seeds)
Exercise and Fall Prevention
- Balance and functional training, with or without resistance training can prevent falls and fractures
- Resistance and impact exercise may improve BMD
- Exercise improves physical functioning or QoL
- Balance exercises: shifting body weight, reacting to balance upset, reducing base of support
- Functional exercises: exercises that improve ability to perform daily tasks or activities
- Resistance exercises: work against resistance (e.g., squats, lunges, push-ups)
Pharmacotherapy Options
- Anti-resorptive agents:
- Bisphosphonates (alendronate, risedronate, zoledronic acid)
- RANKL monoclonal antibody (denosumab)
- Selective estrogen receptor modulator (raloxifene)
- Anabolic agents:
- Parathyroid hormone analog (teriparatide)
- Sclerostin inhibitor (romosozumab)
Approach to Pharmacotherapy
- Bisphosphonates: first-line therapy for most people
- Denosumab: second-line option for those with contraindications or intolerance to bisphosphonates
- Anabolic therapy: for select patients with recent severe vertebral fracture or ≥ 2 vertebral fractures and T-score ≤ -2.5
- Raloxifene: last resort for postmenopausal females who are not at high risk of VTE### Contraindications and Intolerance
- Individuals who cannot take or choose not to take other suggested therapies may consider alternative treatments.
Treatment Duration - Bisphosphonates
- Initial treatment duration: 3-6 years.
- 6-year treatment duration for individuals with a history of hip, vertebral, or multiple non-vertebral fractures, or new/ongoing risk factors for accelerated bone loss.
- Assess adherence and tolerance to therapy.
- Inadequate response or ongoing concerns: extend or switch therapy, seek consultant advice.
- Stop therapy (drug holiday) and reassess after 3 years, or earlier if necessary.
Treatment Duration - Denosumab
- Long-term uninterrupted therapy with 6-month injections is recommended.
- Delaying injections by more than 1 month increases the risk of rapid bone loss and vertebral fractures.
- Therapy duration may be assessed after 6-10 years, with transition to alternative therapy if stopping.
Treatment Duration – Anabolic Therapies
- Teriparatide: daily subcut injections for up to 24 months.
- Romosuzumab: monthly subcut injections for up to 12 months.
- Consultation with an expert is required, and therapy may depend on affordability and feasibility.
Monitoring
- BMD may be repeated at a shorter interval if secondary causes of OP, new fracture, or new clinical risk factors associated with rapid bone loss are present.
Pharmacotherapy Workup
- Use risk assessment tools to determine patient's risk for fractures.
- Consider secondary drug-induced causes, nonpharmacological and pharmacological interventions.
Calcium and Vitamin D
- Calcium benefits and risks include recommending 500-700 mg/day through diet and supplementation, considering type of calcium salt and elemental Ca2+.
- Vitamin D recommendations include considering patient's 25-OH-Vit D level.
Pharmacotherapy Considerations
- Indications, common/rare side effects, contraindications, drug interactions, dosage, and administration issues should be considered.
- Effectiveness, cost, safety, convenience, frequency, and patient adherence to pharmacotherapy should be evaluated.
Summary
- Identification of OP fracture risk factors is key.
- Risk assessment tools include FRAX and CAROC.
- Investigations include biochemical and radiographic measures like BMD, spine X-ray, and VFA.
- Benefit of pharmacotherapy increases with risk.
- Bisphosphonates are first-line therapy for most, with initial duration of 3-6 years.
- Denosumab is an alternative therapy requiring long-term commitment.
- Anabolic agents are for select high-risk patients, with accessibility and feasibility limitations.
- Raloxifene is a last option for females not at high risk for VTE.
- Regular monitoring of therapy is necessary, with reassessment of BMD and fracture risk in 3 years or earlier if necessary.
Calcium and Vitamin D
- Recommended dietary allowance for calcium: 1000 mg/day for men and women aged 51-70 years, 1200 mg/day for men and women over 70 years old
- Recommended dietary allowance for vitamin D: 600 IU/day for men and women aged 51-70 years, 800 IU/day for men and women over 70 years old
- Health Canada recommends 400 IU/day of vitamin D for adults over 50 years old, in addition to dietary sources
Exercise for Fracture Prevention
- Balance and functional training with or without resistance training can prevent falls and may prevent fractures
- Resistance and impact exercise may improve bone mineral density (BMD)
- Exercise may improve physical functioning or quality of life
- Examples of balance exercises: shifting body weight to the limits of stability, reacting to things that upset one's balance, maintaining balance while moving
- Examples of functional exercises: chair stands for sit-to-stand ability, stair-climbing to train for hiking
- Examples of resistance exercises: squats, lunges, push-ups
Nonpharmacologic Interventions
- Balanced diet with a "foods first" approach
- Individualized approach may be needed, consult a dietitian
- If receiving pharmacotherapy, individualize calcium and vitamin D intake
OHIP Coverage of 25-OH Vit D Testing
- Coverage for individuals with malabsorption syndromes, osteopenia, osteoporosis, rickets, renal diseases, and medications affecting vitamin D metabolism
Risk-Based Pharmacotherapy
- Indications for pharmacotherapy: previous hip or spine fracture, or ≥ 2 fragility fracture events
- Pharmacotherapy options: anti-resorptive (bisphosphonates, RANKL monoclonal antibody, SERM) and anabolic (parathyroid hormone analog, sclerostin inhibitor) agents
- Safety and adherence issues: risks of atypical femur fracture and osteonecrosis of the jaw with long-term bisphosphonate use, bone loss and vertebral fracture risk with delayed denosumab dosing or discontinuation
Approach to Pharmacotherapy
- Bisphosphonates: first-line therapy for most people, assess adherence and tolerance
- Denosumab: second-line option, assess contraindications or substantial intolerance to, or barriers to bisphosphonates
- Anabolic agents: upfront therapy for select higher-risk patients, accessibility and feasibility may limit use
- Raloxifene: last option for women, not for individuals at high risk for venous thromboembolism
Pharmacotherapy Considerations
- Indications, efficacy, safety, cost, convenience, and patient adherence to pharmacotherapy
- Monitoring for side effects, contraindications, and drug interactions
- Initial duration of pharmacotherapy: 3-6 years, reassess to resume or stop therapy
Summary
- Identification of osteoporosis fracture risk factors is key
- Risk assessment tools: FRAX, CAROC
- Investigations: biochemical, radiographic (BMD, spine X-ray, vertebral fracture assessment)
- Bisphosphonates: first-line therapy for most, initial duration 3-6 years
- Denosumab: alternative therapy, uninterrupted long-term commitment to treatment
- Anabolic agents: upfront therapy for select higher-risk patients
- Raloxifene: last option for women
- Monitoring of therapy: regularly assess adherence, tolerability, and new risk factors
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Description
Learn about the pathophysiology, clinical presentation, risk factors, and complications of osteoporosis. Review the clinical approach to assessing osteoporosis and use OP Canada guidelines to support clinical decisions.
