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Osteoporosis
Osteoporosis
Robert D. Auerbach, M.D. FACOG Senior Vice President & Chief Medical Officer CooperSurgical, Inc. Associate Clinical Professor Yale University School of Medicine
PATHOGENESIS
DIAGNOSIS TREATMENT
Trabecular bone
Has a light, honeycomb structure Trabeculae are arranged in the directions of tension and compression Occurs in the heads of the long bones Also makes up most of the bone in the vertebrae
Osteons
Principal organizing feature of compact bone
Haversian canal place for the nerve blood and lymphatic vessels Lamellae collagen deposition pattern Lacunae holes for osteocytes Canaliculi place of communication between osteocytes
Bone Cells
Osteocytes - derived from osteoprogenitor cells
Osteoblasts
Osteoclasts
Osteocytes
Trapped osteoblasts
In lacunae
Keep bone matrix in good condition and can release calcium ions from bone matrix when calcium demands increase
Osteocytic osteolysis
Osteoblasts
Make collagen Activate nucleation of hydroxyapatite crystallization onto the collagen matrix, forming new bone As they become enveloped by the collagenous matrix they produce, they transform into osteocytes Stimulate osteoclast resorptive activity
Osteoclasts
Resorb bone matrix from sites where it is deteriorating or not needed Digest bone matrix components
Focal decalcification and extracellular digestion by acid hydrolases and uptake of digested material
Disappear after resorption Assist with mineral homeostasis
Matrix - Osteoid
Collagen type I and IV Layers of various orientations (add to the strength of the matrix)
Mineral
A calcium phosphate/carbonate compound resembling the mineral hydroxyapatite Ca10(PO4)6(OH)2 Hydroxyapatite crystals
Imperfect Contain Mg, Na, K
Phase III
New bone laid down by osteoblasts Takes 3 months
Hormonal Influence
Vitamin D Parathyroid Hormone
Calcitonin
Estrogen Androgen
Vitamin D
Osteoblast have receptors for (1,25-(OH)2-D) Increases activity of both osteoblasts and osteoclasts
Parathyroid Hormone
Accelerates removal of calcium from bone to increase Ca levels in blood PTH receptors present on both osteoblasts and osteoclasts Osteoblasts respond to PTH by
Change of shape and cytoskeletal arrangement Inhibition of collagen synthesis Stimulation of IL-6, macrophage colony-stimulating factor secretion
Chronic stimulation of the PTH causes hypocalcemia and leads to resorptive effects of PTH on bone
Calcitonin
C cells of thyroid gland secrete calcitonin Straight chain peptide - 32 aa
Actions of Calcitonin
Osteoclasts are target cells for calcitonin Major effect of clacitonin is rapid fall of plasma calcium concentration caused by inhibition of bone resorption Magnitude of decrease is proportional to the baseline rate of bone turnover
Androgens
Increase bone formation
Glucocorticoids
Inhibit bone formation
Thyroid hormones
Increase bone resorption
TGF-
Osteoporosis
A disease characterized by:
low bone mass microarchitectural deterioration of the bone tissue
Leading to:
enhanced bone fragility increase in fracture risk
Severe osteoporosis
More than 2.5 SD below with fractures
Osteoporosis - Epidemiology
Disorder of postmenopausal women of northern European descent Increase in the incidence related to decreasing physical activity
Statistics
National Osteoporosis Risk Assessment (NORA): Factors Associated With Increased Risk of Osteoporosis
Osteoporosis
Mechanisms causing osteoporosis
Imbalance between rate of resorption and formation Failure to complete 3 stages of remodeling
Types of osteoporosis
Type I Type II Secondary
Osteoporosis - Types
Postmenopausal osteoporosis (type I)
Caused by lack of estrogen Causes PTH to overstimulate osteoclasts Excessive loss of trabecular bone
Secondary osteoporosis
Osteoporotic Vertebra
Women initiating ET/HT for menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)
Relative Risk
DXA-assessed content is a proven effective method for assessing osteoporosis related fracture risk. Population surveys and research studies demonstrate a decrease in bone density measured by DXA predicts fracture at specific sites.
Marshall, D, et al: Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. British Medical Journal. 312:1254-1259, 1996.
BUA
40 30 20 10 0 Fracture No Fracture
Subjects who developed hip fracture showed significantly (p<0.001) lower heel BUA results in a two-year follow-up prospective study of 1,414 subjects.
Porter, RW, et al: Prediction of hip fracture in elderly women: a prospective study. British Medical Journal. 301:638-641, 1990.
1 0.9
Area Under the Curve
Schott, AM, et al: Ultrasound discriminates patients with hip fracture equally well as dual energy x-ray absorptiometry and independently of bone mineral density.
Journal of Bone and Mineral Research. 10:243-249, 1995.
2.5 2 1.5 1 0.5 0 Hans, et al Bauer, et al Research Study Frost, et al BUA BMD
HRT
SERMS Calcitonin Bisphosphonates