Pharmacotherapy of Osteoporosis - ABCForYourHealth
Pharmacotherapy of Osteoporosis
Marie Meyer, PharmD Candidate 2007
|Epidemiology |Osteoporosis is the most common disease of the bones |
| | |
| |Prevalence: ~55% of the US population over age 50 are at risk (~44 million Americans) |
| |~12% of the US population already have osteoporosis (~10 million Americans) |
| |~43% have low bone mass… may develop into osteoporosis in their lifetime (~34 million Americans) |
| | |
| |Incidence: ~ 1.5 million fractures per year |
| |Location of fractures: vertebrae ~700,000, hip ~300,000, wrist ~250,000, other sites ~300,000 |
| | |
| |Distribution: 80% of cases are in females, 20% in males |
| |People of all ethnic backgrounds are at risk |
| |Females: White and Asian > Hispanic > Black |
| |Males: White and Asian > Black and Hispanic |
|Disease State |Osteoporosis = “porous bone” |
|Definition | |
| |Characteristics: |
| |low bone mass |
| |structural deterioration of bone tissue micro-architecture |
| |decreased bone strength ( bone fragility |
| |increased risk of fractures, especially of the hip, spine, or wrist |
| | |
| |Clinically defined by low bone mineral density (BMD) |
| |Significant clinical outcome fractures of the vertebrae, hips, wrists, and other bones |
|Patho-physiology |Bone remodeling: the constant process of bone formation and resorption. |
| | |
| |Bone development: in children and adolescents bone formation exceeds bone resorption |
| | |
| |Peak bone mass: bone is at maximum density and strength, occurs around age 25-30 |
| | |
| |Bone loss occurs when bone resorption exceeds bone formation, typically after age 30 |
| |Post-menopausal estrogen deficiency accelerates the age-related bone formation/resorption imbalance |
| |Other risk factors (below) also accelerate bone loss or cause a low peak bone mass |
| | |
| |Adult bone mass = peak bone mass – subsequent bone loss |
| | |
| |Increased bone loss or low peak bone mass ( low bone density |
| |Low bone density ( increased risk of fractures |
|Clinical Presentation |“silent disease”… often undiagnosed until fragility fracture occurs |
| | |
| |fragility fracture = bone fracture occurring in the absence of trauma or from very mild trauma |
| |( disability |
| |pain |
| |deformity |
| | |
| |vertebral compression fractures ( internal organ crowding, disability, pain, increased mortality |
| |( changes in body appearance… height loss |
| |curved shoulders and back |
| |thickened waistline |
|Risk Factors |Age |
| |risk increases with age beyond 30 |
| |Gender |
| |menopause causes women to lose bone mass faster than men |
| |PMH |
| |history of fracture as an adult (fragility or traumatic fractures) |
| |history of recent falls |
| |early onset estrogen deficit (< 45 years old) |
| |visual impairment |
| |dementia |
| |general poor health |
| |FH |
| |1st degree relative with history of fragility fracture |
| |Race |
| |Caucasian and Asian women are at the greatest risk |
| |Black and Hispanic women also have a significant risk |
| |Bone structure |
| |small body frame increases risk |
| |osteopenia = low bone mass |
| |Body weight |
| |< 127 lbs (< 57.7 kg) increases risk |
| |Medications |
| |*steroids* (glucocorticoids, andrenocorticotropin) |
| |anticonvulsants (phenobarbital, phenytoin) |
| |aluminum antacids |
| |cholestyramine |
| |cytotoxic drugs (methotrexate) |
| |estrogen antagonist (tamoxifen – before menopause) |
| |gonadotropin releasing hormone (GnRH) |
| |heparin (long-term use) |
| |immunosuppresants (cyclosporine A) |
| |lithium |
| |thyroid hormones (thyroxine in excessive doses) |
| |Lifestyle factors |
| |current smoking |
| |excessive EtOH intake (>2 drinks daily) |
| |lifelong inadequate calcium intake |
| |physical inactivity |
|Diagnosis |Bone mineral density (BMD) measurement |
| |lower BMD correlates with higher fracture risk |
| |Hip BMD = best predictor of hip fractures, also predicts fractures at other sites |
| | |
| |Z-score = expected BMD for age and sex of the patient |
| |T-score = expected BMD for young normal adults of the same sex as the patient |
| | |
| |Normal = T-score ≥ –1 = BMD within 1 standard deviation (SD) of “young normal” |
| | |
| |Osteopenia = T-score between –1 and –2.5 = BMD between 1 and 2.5 SD less than “young normal” |
| | |
| |Osteoporosis = T-score ≤ –2.5 = BMD 2.5 or more less than “young normal” |
| | |
| |Established osteoporosis = T-score ≤ –2.5 plus history of fragility fracture |
| | |
|Diagnosis | |
|Continued |BMD Measurement Techniques |
| |Dual x-ray absorptiometry (DXA) |
| |Central DXA – spine, hip, or wrist (diagnosis & monitoring) |
| |**** Spine or hip central DXA is the standard diagnostic technique **** |
| |Peripheral DXA – forearm, finger, heel (screening) |
| |Single-energy x-ray absorptiometry (SXA) – forearm, finger, heel (screening) |
| |Quantitative computed tomography (QCT) – central or peripheral (diagnosis & monitoring) |
| |Ultrasound densitometry – heel, tibia, patella, or other peripheral sites. |
| |Not as precise as DXA or SXA, but good prediction of fracture risk (screening) |
| |BMD testing should be performed on: |
| |All women ≥ 65 |
| |Postmenopausal women < 65 with one or more risk factors (other than race, gender, postmenopausal) |
| |Postmenopausal women with fractures (confirm diagnosis, determine disease severity) |
| | |
| |Treatment to reduce fracture risk is recommended for women with |
| |T-scores < –2.0 by hip DXA without risk factors |
| |T-scores < –1.5 by hip DXA plus ≥ 1 risk factors |
| |prior vertebral or hip fracture |
|Desired Therapeutic |Osteoporosis prevention goals* |
|Outcomes* |Optimize skeletal development and maximize peak bone mass at skeletal maturity |
| |Prevent age-related and secondary causes of bone loss |
| |Preserve the structural integrity of the skeleton |
| |Prevent fractures |
| |Osteoporosis treatment goals* |
| |Prevent fractures |
| |Stabilize or achieve an increase in bone mass |
| |Relieve symptoms of fractures and skeletal deformity |
| |Maximize physical function |
| | |
| |*American Association of Clinical Endocrinologists Medical Guidelines For Clinical Practice For the Prevention and Treatment of |
| |Postmenopausal Osteoporosis: 2001 Edition, with selected updates for 2003 |
|Treatment Options** |Non-pharmacologic |
| |adequate calcium/vitamin D intake and good nutrition in general |
| |calcium ~1000-1200mg daily |
| |vitamin D ~400-800 IU daily |
| |regular weight bearing exercise |
| |fall prevention – vision, hearing, neurological defects, medication side effects, home safety, walking aids |
| |fall protection – hip protective garments |
| |alcohol moderation and tobacco abstinence |
| | |
|**See Treatment Options|Pharmacologic |
|Table |therapeutic class generic drug (Brand) |
| |bisphosphonates alendronate (Fosamax), ibandronate (Boniva), risedronate (Actonel) |
| |calcitonin (Miacalcin, Fortical) |
| |estrogen therapy (Climara, Estrace, Estraderm, Ogen, Ortho-Est, Premarin, Vivelle) |
| |hormone therapy (Activella, Femhrt, Premphase, Prempro) |
| |parathyroid hormone teriparatide (Forteo) |
| |selective estrogen raloxifene (Evista) |
| |receptor modulator |
| | |
| | |
| | |
|Monitoring |Efficacy |
| |DXA every 1-2 years (note that fracture risk may decrease without noted increase in BMD) |
| |Height yearly |
| |Patient reported fall, fracture, bone pain monthly or weekly |
| | |
| |Toxicity |
| |Bisphospinates |
| |Alendronate – serum calcium and phosphorus |
| |patient reported dyspepsia, heartburn, acid reflux, dysphagia |
| |physical exam for GERD, esophagitis, esophageal ulcer, gastritis, gastric ulcer |
| |Ibandronate – serum creatinine before each IV dose, serum calcium, phosphorus, and magnesium, |
| |patient reported dyspepsia |
| |physical exam for esophagitis, gastritis, ulcer |
| |Risedronate – alkaline phosphates, serum calcium, phosphorus, and potassium |
| |patient reported dyspepsia, heartburn, acid reflux, dysphagia |
| |physical exam for esophagitis, gastritis, ulcer |
| | |
| |Calcitonin |
| |serum calcium |
| |patient reported rhinitis, nosebleeds, sinusitis |
| |physical exam for nasal ulceration |
| | |
| |Estrogen |
| |patient reported chest pain, SOB, hemoptysis, cardiac awareness, one-sided weakness, sudden visual or speech problems, sudden confusion or |
| |dizziness, sudden severe headache, claudication, leg warmth/ redness/ swelling |
| | |
| |Hormone therapy |
| |mammogram yearly |
| |patient reported chest pain, SOB, hemoptysis, cardiac awareness, one-sided weakness, sudden visual or speech problems, sudden confusion or |
| |dizziness, sudden severe headache, claudication, leg warmth/ redness/ swelling |
| |patient reported unusual vaginal bleeding |
| | |
| |Teriparatide |
| |calcium, BP, uric acid |
| | |
| |Raloxifene |
| |CBC, lipid profile |
| |patient reported claudication, leg cramps, leg warmth/ redness/ swelling of the leg, hot flashes, leg cramps |
References
American Association of Clinical Endocrinologists Medical Guidelines For Clinical Practice For the Prevention and Treatment of Postmenopausal Osteoporosis: 2001 Edition, with selected updates for 2003
Physician’s Guide to Prevention and Treatment of Osteoporosis, National Osteoporosis Foundation, 2003
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