PHARM - Osteoporosis PDF

MPAP 517: Osteoporosis Wednesday, February 21, 2024 Emily Ghassemi, PharmD, BCACP, CDCES, CPP Clinical Assistant Professor – Campbell University CPHS Clinical Pharmacist Practitioner – Coats Medical Services [email protected] Pharmacotherapy: Principles and Practice Osteoporosis: Chapter 57 Obje...

MPAP 517: Osteoporosis Wednesday, February 21, 2024 Emily Ghassemi, PharmD, BCACP, CDCES, CPP Clinical Assistant Professor – Campbell University CPHS Clinical Pharmacist Practitioner – Coats Medical Services [email protected] Pharmacotherapy: Principles and Practice Osteoporosis: Chapter 57 Objectives 1. Discuss the mechanism of action, indications, therapeutic course, contraindications, drug-drug and drug-food interactions, side effects, and monitoring parameters of the pharmacologic agents commonly used in the treatment of osteoporosis and osteopenia. 2. Discuss the goals of treatment for osteoporosis and osteopenia. 3. Recommend daily calcium and vitamin D intake. 4. Develop an evidence-based treatment plan for a patient with osteoporosis or osteopenia based on patient specific factors. 5. Develop an appropriate monitoring plan for a patient being treated of osteoporosis and osteopenia based on patient specific factors. 6. Counsel a patient on non-pharmacologic treatment options to prevent bone loss. 7. Identify pharmacologic agents known to cause bone loss. Guidelines Bone Health and Osteoporosis Foundation (BHOF), formally the National Osteoporosis Foundation (NOF) o LeBoff MS, Greenspan SL, Insogna KL et al. The clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int. 2022;33(10):2049-102. o Focus on postmenopausal women and men > 50 years American Association of Clinical Endocrinologists (AACE) o Camacho PM, Petak SM, Binkley N, et al. American Association of Clinical Endocrinologist/American College of Endocrinology Clinical Practice Guidelines for the Diagnosis and Treatment of Postmenopausal Osteoporosis – 2020 Update. Endocr Pract. 2020;26(Suppl 1):1-46. o Focus on postmenopausal women Significance & Impact HTN : Stroke :: Osteoporosis : Fracture ↑ Mortality up to 20% during two years following fx > 50% hip fx survivors unable to return to independent living < 25% receive treatment within one year after hip fx Wilk et al. Osteoporos Int. 2014. Camacho et al. AACE 2020. Endocr Pract. Pathophysiology  MOA Drug OsteoCLASTS OsteoBLASTS Resorption / Breakdown (chew) Bone formation (build) Treatment goals  Prevent fractures  Maintain (or increase) bone mineral density (BMD)  Prevent secondary causes of bone loss  Reduce morbidity/mortality associated with osteoporosis Screening  BMD measurements recommended in: 1. Women ≥ 65 years and Men ≥ 70 years 2. Peri-menopausal women and men aged 50-69 with risk factors 3. Anyone with fracture > 50 years 4. Adults with secondary cause for osteoporosis (e.g., hyperparathyroidism, chronic glucocorticoid treatment) Prevention & Lifestyle PREVENTION: Medications associated with bone loss  GLUCOCORTICOIDS o ≥ 5 mg/day prednisone for ≥ 3 months  Anticonvulsants (e.g., phenytoin, carbamazepine)  Depo-medroxyprogesterone  Chemotherapeutic drugs  Proton pump inhibitors (PPIs)  Methotrexate PREVENTION: Non-pharmacologic therapy/modifiable risk factors  Smoking cessation  Adequate Calcium / Vitamin D intake  Sufficient nutrient intake / appropriate weight maintenance  Weight-bearing exercise  Limit heavy alcohol use  Fall prevention Bone health: Calcium   Common calcium-containing foods: o Milk (8oz) = 300 mg o Yogurt (6oz) = 180 mg o Cheese (1oz) = 200 mg o Spinach (1 c) = 250 mg o Almonds (1oz) = 75 mg o Typical daily intake from other, non-dairy sources = 250 mg 1200 Adults ≥ 50 years should intake _____ mg (elemental) calcium daily o Ideally, consumed from diet o Max absorbed at one time = 500-600 mg o Intake per day should not exceed 1,500 mg Bone health: Calcium  Supplementation adverse effects o  Constipation, nausea Contraindications/Precautions o Hypercalcemia o Kidney stones o Many drug interactions (e.g., antibiotics, thyroid medications) Calcium supplement products Products Elemental calcium Cost Administration FYI Carbonate Citrate Tums, Caltrate, Os-Cal, Viactiv Calcitrate, Citracal 1 g = 400 mg 1 g = 211 mg $6-10 $13-17 Independent of food; preferred with PPI Take with food Caution: Label Caution: Label Caution: Label Bone health: Vitamin D   Vitamin D: o Needed for calcium absorption o Also data to reduce falls! o 800-1000 Recommended intake _________ IU (international units) daily o Max recommended dose for chronic use = 4,000 IU / day Measure 25-hydroxyvitamin D levels in patients at risk for deficiency o 30-50 ng/mL = normal Vitamin D o 20-29 ng/mL = Vitamin D insufficient o ≤ 20 ng/mL = Vitamin D deficient Bone health: Vitamin D    Vitamin D2 (ergocalciferol) o Plant source (may be preferred by strict vegetarians/vegans) o Use of high dose D2 (50,000 IU weekly) no longer supported by AACE 2020 Vitamin D3 (cholecalciferol) o Most from animal source o Available OTC Recommended supplementation doses: o Recommended Vitamin D intake for all (prevention): 800-1,000 IU daily o For vitamin D insufficiency / deficiency: 5,000 IU daily x 8-12 weeks – Goal to achieve level > 30 ng/mL – Maintenance: 1,000-2,000 IU daily to maintain target level Patient case  72-year-old, post-menopausal cisgender female with osteopenia. Patient reports eating cereal with a serving of milk and yogurt daily. ~300 mg ~180 mg Non-dairy sources (~250 mg)  Goal calcium and vitamin D intake?  Does the patient require calcium supplementation?  What if current 25-OH Vitamin D level = 18 ng/mL. Treatment Who qualifies for pharmacologic treatment:  All individuals > 50 years with any of the following: o History of hip / vertebral fracture o T-score ≤ -2.5 at femoral neck or spine o Osteopenia (T-score -1.0 to -2.5) and 10-year probability (FRAX) – ≥ 3% hip fracture OR – ≥ 20% major osteoporosis-related fracture FRAX 10-year risk calculator   Fracture Risk Assessment Tool o Developed to evaluate fracture risk o Developed from population-based cohorts from Europe, North America, Asia, and Australia o Gives 10-year probability of hip fracture and major osteoporotic fracture (e.g., spine, forearm, shoulder) https://www.sheffield.ac.uk/FRAX/tool.aspx?country=9 Patient case   71-year-old African American/Black male without risk factors: o 158 lbs o 67 inches o BMD T-score R hip = -2.2 Calculate FRAX score. ii. What if patient had previous fracture? iii. What if patient were female & previous fracture? iv. History of RA? v. Asian American? Caucasian? Inhibits osteoClasts (↓boneoptions resorption/chew) Treatment Stimulates osteoBlasts (↑bone formation/build) Bisphosphonates Fosamax (alendronate), Actonel (risendronate), Reclast (zoledronic acid), Boniva (ibandraonte) RANKL inhibitor Prolia (denosumab) Estrogen agonist/antagonist PTH analogues Forteo (teriparatide) Tymols (abaloparatide) Evista (raloxifene) Estrogens Calcitonin Sclerostin inhibitor (Evenity/romosozumab). Fracture risk reduction First-line treatment options  Bisphosphonates (except ibandronate) o Fosamax® (alendronate) o Actonel®, Atelvia® (risendronate) o Reclast® (zolendronic acid)  RankL inhibitor o Prolia® (denosumab) Bisphosphonates  Mechanism – Inhibits bone resorption (osteoclast)  increases BMD will lower calcium  Contraindications: Hypocalcemia; Esophageal stricture or inability to sit/ stand upright x30mins (PO formulations); eGFR < 30-35  Adverse effects: o Common: Gastrointestinal (impaired swallowing, esophageal inflammation); Hypocalcemia (18%, transient) o Serious: Renal insufficiency, atypical fractures, osteonecrosis of the jaw (ONJ) o Formulation specific (infusion): Acute-phase reaction – Pre-treat with APAP; observe for one hour – IV infusion contraindicated in CrCl < 35 pre-treat with tylenol due to acute-phase reaction Bisphosphonate oral administration    Monitoring o SCr (CrCl) o Calcium and 25(OH) Vitamin D Kinetics: o Bioavailability: 0.6% oral o Half-life: 10 years Oral bisphosphonate counseling: o Take first thing in the morning on an empty stomach (≥ 30 minutes before food/beverage/other medications) o Take with 8oz water o Sit upright for 30 minutes after administering Controversial adverse reactions   Osteonecrosis of the jaw (ONJ) o Rare ( -2.5 and patient has remained fx-free) o Holiday after 5 years PO bisphosphonate o Holiday after 3 years IV bisphosphonate In high-risk: o Holiday after 6-10 years PO bisphosphonate o Holiday after 6 years IV bisphosphonate  May end holiday based on individual (e.g., ↑ fracture risk, ↓BMD)  Holiday NOT recommended for nonbisphosphonate drugs Camacho et al. AACE 2020. Endocr Pract. Bisphosphonates Alendronate (Fosamax®) Frequency Weekly Tablets, Dosage forms Effervescent, Solution Risendronate (Actonel®, Atelvia®) Weekly OR Monthly Tablets Fracture ↓ 50% (all) 49% spine 36% other Wait 30 minute 30 minute Zoledronic acid Ibandronate (Reclast®) (Boniva®) Annually Monthly IV over 15 minutes yearly Tablets or IV q 3 months 70% spine 41% hip 25% other N/A 50% spine 1 hour Prolia (denosumab)  Mechanism – Binds to nuclear factor-kappa ligand (RANKL) to block binding to receptor  Inhibits osteoclast formation  increases BMD  Contraindications: Hypocalcemia; Pregnancy  Administration: 60 mg subQ injection every 6 months o ~$1,200 per injection o No dosage adjustment for renal Prolia (denosumab)  Monitoring: Calcium, magnesium, phosphorous  Adverse effects: o Common: Dermatologic (rash/dermatitis, eczema) (11%); hypertension (4%); hyperlipidemia (7%); upper respiratory infection (5%) o Serious: Atypical fractures, osteonecrosis of the jaw (ONJ) (3% hip or >20% major osteoporosis-related) First line options: Alendronate, Risedronate, Zoledronic acid, and Denosumab Oral bisphosphonates are good and effective options, but require strict administration technique Alternative therapies reserved for high-risk patients unresponsive to first-line treatments or those with concomitant indications MPAP 517: Osteoporosis Emily Ghassemi, PharmD, BCACP, CDCES, CPP [email protected]