Dec 23, 2015
OsteoporosisAhmed Shaman
Department of Clinical [email protected]
Background Reading & References
• Drugs for Postmenopausal Osteoporosis. Treatment Guidelines from The Medical Letter 2008:6(74);67-74.
• Sundeep Khosla, M.D., and L. Joseph Melton III, M.D., M.P.H. Osteopenia. N Engl J Med 2007;356:2293-300.
• Dipiro Chapter 93
Introduction
• Osteoporosis is a common and often silent disorder causing significant morbidity and mortality and reduced quality of life
• It is associated with increased risk and rate of bone fracture • Common sites of fracture include the spine, hip, and wrist• The fractures associated with osteoporosis have an enormous impact
on individual patients • Acute pain• Chronic pain• Loss of mobility• Height loss• Depression • Nursing home placement• Death
Physiology & pharmacology of bone formation
Physiology & pharmacology of bone formation
Bone Mineral Density
Measurement of Bone Mineral Density
• Bone mineral density can be measured at various sites throughout the skeletal system
• Central (hip and/or spine)• Peripheral (heel, forearm, or hand)
• Various methods• Dual-energy x-ray absorptiometry (DXA)
• central and peripheral sites• Quantitative ultrasound• Peripheral quantitative computed tomography• Radiographic absorptiometry• Single-energy x-ray absorptiometry
• Central DXA is recommended for diagnosis due to inconsistencies in T-scores measured between different sites and by different methods
Peripheral sites
Interpreting BMD Data
• T-scores and Z-scores are used• T-score is the number of standard deviations from the mean bone
mineral density in healthy young white women• The Z-score is a similar measure that is corrected for age and gender
of the patient
Skeletal Disorders T-scores
Normal ≥ -1
Osteopenia Between -2.5 and -1.0
Osteoporosis < -2.5
Clinical Presentation and Diagnosis of Osteoporosis
• General• Many patients with osteoporosis are asymptomatic unless they experience a
fragility fracture
• Symptoms• Symptoms of fragility fracture include pain at the site of the fracture or
immobility
• Signs• Height loss (greater than 2 cm)• Spinal kyphosis (“dowager’s hump”)• Fragility fracture especially of the hip or spine
• Laboratory Tests• Lab tests are only useful to rule out secondary causes of osteoporosis
• Diagnostic Tests• Bone densitometry using DXA reveals a T-score at least -2.5 SD below the
mean
Laboratory Evaluation
• Identifying or excluding secondary causes• Hyperparathyroidism • Low 25-hydroxyvitamin D levels• Hyperthyroidism• Cancer
TREATMENT
• Pharmacologic and nonpharmacologic therapies are aimed at:
1. Preventing fractures and their complications2. Maintaining or increasing bone mineral density3. Preventing secondary causes of bone loss4. Reducing morbidity and mortality associated with
osteoporosis
Treatment
• Lifestyle modification• Calcium• Vitamin D• Bisphosphonates
• Alendronate• Risedronate• Ibandronate• Zoledronic Acid
Treatment (2)
• Hormonal Therapy• Raloxifene• Estrogen• Calcitonin• Parathyroid Hormone• Testosterone in some men
Lifestyle Modification
Drugs Causing Fall
•Medications associated with increased risk of falling• Drugs affecting mental status
• antipsychotics, benzodiazepines, tricyclic antidepressants, sedative/hypnotics, anticholinergics, and corticosteroids
• Drugs causing orthostatic hypotension• Some cardiovascular and antihypertensive
Calcium & Vitamin D
• Elderly patients or patients receiving proton pump inhibitors or H2-receptor antagonists may have added difficulty absorbing calcium supplements due to reduced stomach acidity→ Ca citrate or Ca acetate more soluble
Over 65 years Adults under 65 years
Calcium 1,500 mg / day 1,000 mg / day
Vitamin D 800 – 1,000 IU / day 400 – 800 IU / day
Calcium Adverse Events
• Constipation, bloating, cramps, and flatulence• Changing to a different salt form may alleviate
symptoms for some patients • Calcium salts may reduce the absorption of
• Iron• Some antibiotics, such as tetracycline and
fluoroquinolones (up to 50%)• Thyroid hormone• → separate time of administration
Bisphosphonates
• Bisphosphonates are first-line therapy for osteoporosis due to established efficacy in preventing hip and vertebral fractures
• Decrease bone resorption by binding active sites & inhibiting osteoclasts
• IV & PO formulations
Bisphosphonates
Bisphosphonates – Adverse Effects
• Oral: heartburn, esophageal irritation & esophagitis.• Must take with about 180–240 mL of water after
overnight fast & in upright position • Afterwards stay upright 30-60 minutes & don’t take
anything by mouth except water• IV: infusion reactions, atrial arrhythmias• Either (especially IV & with chronic use)
• Osteonecrosis of the jaw• Risk factors include
• Chemotherapy, radiotherapy, corticosteroids, infection or pre-existing dental disease
Bisphosphonates
• Bisphosphonates are not recommended for use in patients with esophageal abnormalities, hypocalcaemia, renal insufficiency or failure (creatinine clearance less than 30–35 mL/min)
• Bisphosphonates should not be taken with other medications or dietary supplements(↓absorption)
Bisphosphonates
Hormones
•Raloxifene: • Selective estrogen receptor modulator (SERM)
• Estrogen-like effects on bone (reduce bone resorption and decrease overall bone turnover)
• Prevents & treats osteoporosis, ↓ vertebral fractures by 30%• AE: Hot flashes, leg cramps & edema• Increase risk of thrombosis• Increase risk of fatal stroke
Hormones
•Estrogen (HRT)• Replacement in postmenopausal women• Prevents hip and veterbral fractures by 33%• Give with progestin if intact uterus to prevent
endometrial cancer• No longer recommended due to adverse effects
• Increase risk of cardiac death, MI, stroke, pulmonary embolism & breast cancer
• WHI and HERS studies
Other Pharmacotherapy
• Calcitonin• Inhibits osteoclasts• IM, SC (neutralizing antibodies) and intranasal• Treatment; causes nasal irritation• AEs including flushing, urinary frequency, nausea, vomiting, abdominal
cramping, and irritation at the injection site
• Teriparatide• Parathyroid Hormone, stimulates bone formation• Risk of hypercalcemia, orthostatisc hypotention • Treatment; black box warning for osteosarcoma
Treatment Overview
• For everyone• Calcium, Vitamin D
• Osteopenia (T score – 1.0 to 2.49)• Add Lifestyle Modification• Consider pharmacotherapy risk vs benefit
• Osteoperosis (T score - 2.5 or more)or fracture
• Add pharmacotherapy (likely bisphosphonate)