Medicine Ch 76 802-810
Osteoporosis
-most common bone disorder of bone and mineral metabolism, characterized by compromised
bone strength, predisposing a person to increased risk for fracture
-bone strength reflects 2 features: bone density and bone quality
-bone density is the peak adult bone mass and amount of bone lost during adulthood
-bone quality is bone architecture, bone geometry, bone turnover, mineralization
Epidemiologic Factors – 1.5million osteoporotic fractures occur each year
-hip fractures have the most serious consequences with mortality of 20% within 1st year, mostly
in women and lifetime risk is 17% for hip fracture
Risk Factors – history of fracture in adulthood, smoking, and oral corticosteroid use >3mo
Peak Bone Mass/Loss – determined by genetic factors; men have higher bone mass than ladies,
AA and Hispanics have more bone mass than Caucasians
-vitamin D receptor alleles, estrogen receptor alleles, and high bone mass gene are associated
-pattern of bone loss differs for males and females; bone loss greater in sites rich trabecular
bone (spine) than in cortical bone (femoral neck)
-estrogen deficiency influences cytokines which affect osteoblastic/clastic activity and bone
turnover, and skeletal integrity is further influenced by Ca intake, Vit D intake, activity, weight
-may secondary causes of bone loss have been found, such as excess thyroid hormone,
glucocorticoids, antiseizure medications, heparin, gonadotropin-releasing hormone agonists,
aromatase inhibitors, depo-medroxyprogesterone, hypogonadism, and hyperparathyroidism
-all patients should have a workup of serum calcium, vitam D, alkaline phosphatase for Paget
disease, malignancy, cirrhosis, or vitamin D deficiency, liver/renal tests thyrotropin, urine
calcium and creatinine,
Clinical Manifestations – considered a silent disease until fractures occur in the hip (90% after a
fall) or in the spine which causes back pain
-spinal fractures may cause height loss, kyphosis, and severe cervical lordosis (dowager’s hump)
Diagnosis – made following an acute clinical fracture or with bone mineral densitometry scans
Bone Mineral Density – defines osteoporosis as bone mineral density 2.5 SD below adult peak
bone mass (T-score <-2.5 SD)
-osteopenia (low bone mass) is defined as bone mass measurement between -1.0 and -2.5
standard deviations (T score -1 to -2.5)
-normal bone density is defined as assessment above 1.0 SD below adult peak bone mass (T
score > -1.0)
-GOLD STANDARD for bone mineral density is dual-energy x-ray absorptiometry (DXA) of the
hip and the spine and use the lowest value
-in patients with hyperparathyroidism, forearm DXA should be assessed
Prevention – include calcium and vitamin D supplementation, exercise, and fall prevention
-1200mg of calcium for postmenopausal women
-vitamin D comes from diet and photosynthesis; low vitamin D can lead to secondary
hyperparathyroidism (Ca absorption limited, parathyroid secretes PTH)
-exercise is important for maintaining skeletal integrity
Treatment – bisphosphonates are mainstay of osteoporosis prevention and treatment by
inhibiting cholesterol synthesis pathway in osteoclasts to cause early apoptosis, inhibit
osteoclast migration and attachment (alendronate, risedronate, ibandronate, zolendronate)
-risedronate for men, ibandronate for postmenopausal osteoporosis, alendronate for men and
patients with glucocorticoid-induced osteoporosis, zolendroic acid is post-menopausal
osteoporosis
-oral bisphosphonates are poorly absorbed and must be taken in the morning on an empty
stomach and must not seat for 60 minutes or lie down
Estrogen Agonists-Antagonists – raloxifene is approved for prevention and treatment of
osteoporosis, not associated with endometrial hyperplasia; small risk of DVT or PE
Calcitonin can treat postmenopausal osteoporosis
Parathyroid Hormone can increase bone-mineral density (Teriparatide)
-receptor activator of NF-kB (RANK) and RANKL are mediators of osteoclast activity, and an
antibody to RANKL reduces osteoclast activity and decreases resorption = increased bone mass
Verterbroplasty involves injection of cement into compressed vertebra
-kyphoplasty involves injection of balloon into vertebral body and fill it with cement