Peggy Cawthon, M.P.H Physiology of Aging May 3 rd, 2004
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1 Peggy Cawthon, M.P.H Physiology of Aging May 3 rd, 2004 pcawthon@psg.ucsf.edu
2 Lecture Outline Basic definitions Changes in calcium metabolism with aging Hormone regulation of bone metabolism Epidemiology of osteoporosis & fractures Osteoporosis in men What a DXA bone density scan tell us a real world example Treatment
3 Definitions
4 Definitions Osteoporosis, or porous bone, is a disease characterized by low bone mass and structural deterioration of bone tissue, leading to bone fragility and an increased susceptibility to fractures. National Osteoporosis Foundation (
5 Definitions Bone Mineral Density (BMD): a measure of the mineral content of bone per volume, usually estimated through a DXA scan and expressed as grams per cubic centimeter (g/cc). Also referred to as bone mass.
6 Definitions Composition of bone: 35% organic components (cells, fibers, collagen, etc.) 65% inorganic mineral salts (mostly calcium phosphate)
7 Definitions Cell Types: Osteoblasts: form new bone (build) Osteoclasts: resorption of old bone (chew) Osteocytes: mature bone cells that maintain the bone matrix Osteogensis is the formation of new bone
8 Definitions Periosteum is a membrane of connective tissue that covers the outer surface of the bone Endosteum a thinner membrane covering the inner bone surfaces (that is, the trabeculae) Both contain both osteoclasts and osteoblasts
9 Definitions Types of bone: compact bone (also known as cortical bone) spongy bone (also known as trabecular or cancellous bone) Small pieces of bone in the spongy part are called trabeculae
10 Figure 21-1
11 Definitions Bone remodeling is the formation and break down of bone Resorption is the break down of bone Bone is constantly remodeled Why is bone remodeled? To maintain concentrations of Ca 2+ and PO 4 3- To respond to mechanical stress
12 Bone Remodeling Sequence
13 Definitions Microarchitecture of bone A trabeculae
14 Calcium Metabolism
15 Calcium Metabolism Extracelluar calcium levels are highly regulated Need for calcium increases with age Young adults: 800 mg Women over age 50: 1500 mg Increased calcium needs may be explained by worsening absorption of dietary calcium
16 Calcium Metabolism Parathyroid hormone Increases bone resorption, thus elevating plasma calcium Calcitonin Lowers circulating calcium by inhibiting bone resorption Calcitriol (Vitamin D3) Increases calcium absorption in intestine, decreases renal excretion and enhances bone resorption
17
18 Hormone Regulation of Bone Metabolism
19 Hormone Regulation of Estrogen Bone Metabolism Is likely to be protective against resorptive effects of parathyroid hormone Obese women have greater bone mass Might be due in part to higher levels of circulating estrogen Heavier women have greater mechanical stress on their bones
20 Hormone Regulation of Bone Metabolism Glucocorticoids Lower plasma calcium levels, which in turn may cause increased bone resorption, leading to osteoporosis Growth hormone Net increase in calcium absorption and stimulates protein synthesis in bone
21 Hormone Regulation of Bone Metabolism Thyroid hormones Induce hypercalcemia and hypercalciuria and may induce osteoporosis Insulin Promotes bone formation (but there is bone loss among diabetics)
22 Epidemiology of Fractures & Osteoporosis
23 Epidemiology of Fractures & Osteoporosis Skeletal fragility Falls Fractures
24 Epidemiology of Fractures & Osteoporosis One in two women and one in four men over the age of 50 will have an osteoporosis-related fracture 1 to 1.5 million osteoporotic fractures occur annually, including 300,000 hip fractures Osteoporotic fractures cost $17 billion dollars in 2001
25 Epidemiology of Fractures & Osteoporosis Osteoporotic fractures 1,000,000+ Heart attack 513,000 Stroke 228,000 Breast cancer 182,000 Uterine cancer 32,800 Ovarian cancer 26,600 Cervical cancer 15,800 Am J Med 1993, American Heart Association 1995, American Cancer Society 1991
26 Epidemiology of Fractures & Osteoporosis Cooper et al. JBMR 1992
27 Epidemiology of Fractures & Osteoporosis Who is at risk? Smokers Current low bone mass Women Small (thin, short) frame Estrogen deficiency Low lifetime Ca 2+ intake Vitamin D deficiency An inactive lifestyle Excessive use of alcohol Being Caucasian or Asian Involuntary weight loss
28 Epidemiology of Fractures Genetics & Osteoporosis Family history of fracture increases risk by about 2X Over 60% of bone mass is inherited Search for common genes: unsuccessful so far.
29 Epidemiology of Fractures & Osteoporosis ALL types of fractures increase with decreasing BMD Except fractures of face and fingers. Fractures due to severe trauma are osteoporotic. are related to low BMD Indicate an increased risk of future low trauma fractures
30 Epidemiology of Fractures & Osteoporosis Annual consequences of hip fractures 24% will die from complications 25% will require long-term care
31 Epidemiology of Fractures & Osteoporosis Vertebral fractures Hunched over posture loss of height NOT normal aging Most vertebral fractures occur between T6 and L3
32 Osteoporosis in Men
33 Osteoporosis in Men
34 Osteoporosis in Men Men have about ½ the risk of fracture Develop greater bone mass during growth. Larger bones Higher BMD No menopause with accelerated bone loss?
35 Osteoporosis in Men Men have worse outcomes after hip fracture than women One year mortality after hip fracture is twice as high for men as women 20% of those with osteoporosis are men
36 The DXA Scan
37 A DXA scan... Dual Energy X-ray Absorptiometry
38
39 A DXA scan A picture of the hip Estimates of volumetric BMD using a two dimensional picture Also done for the whole body and spine
40 A DXA scan... BMD value is compared to a normal, or reference, population The normal population can be either age-matched or a young population Young population is generally ~30 year old (when bone mass is highest)
41 A DXA scan... T-score is used to diagnose disease Normal: T-score higher than 1 Osteopenia (low bone mass): T-score between 1 and 2.5 Osteoporosis: T-score of 2.5 or less This is the World Health Organization criteria
42 A DXA scan... Young normal population gives a T-score T-score = (individual BMD level young normal mean) Standard deviation of young normal population Age-matched normal population gives a Z-score Z-score = (individual BMD level age matched mean) Standard deviation of age matched population
43 A DXA scan T-score Used for diagnosis of osteoporosis As with the picture, also done for the whole body and spine +
44 Other methods to measure BMD Ultrasound QCT Emerging technologies
45 Treatment Bisphosphonates Alendronate (Fosamax) and Residronate (Actonel) Prevent bone breakdown; maintain or increase BMD; decrease risk of spine fracture and hip fracture Side effects: stomach irritation Selective Estrogen Receptor Modulators (SERMs) Raloxifene (Evista) Maintains/increases BMD; decreases vertebral fracture risk; reduces breast cancer risk Side effects: Leg cramps (occasionally), blood clots (unusual), worse hot flashes
46 Treatment Estrogen Increases bone density; may reduce fracture risk; effects on many other organs Side Effects: Many heart disease, others Calcitonin (Miacalcin) Prevents bone breakdown, helps maintains BMD; not clear how much it reduces fracture risk Nasal irritation?
47 References Physiological Basis of Aging and Geriatrics Human Anatomy, Elaine N. Marieb and Jon Mallatt, editors National Osteoporosis Foundation,
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