谢瑞满骨质疏松症eng

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,*,Chapter,28,Osteoporosis,Presentation: 2005,Rui-man,Xie，Ph.D., M.D.,Professor of Neurology & Gerontology,ZhongShan Hospital, Fudan University,rmxi, xieruima,1,Objective,1、,Definition,、,types and mechanism of,osteoporosis,2,、,Diagnosis,、,prevention and treatment of,osteoporosis,3,、,Etiology and Epidemiology of,osteoporosis,times 45 minutes,2,2,Overview,Definition :,Osteoporosis is a bone disease in which the amount of bone is decreased and the structural integrity of trabecular bone is impaired. Cortical bone becomes more porous and thinner. This makes the bone weaker and more likely to fracture.,3,figures,4,Associated changes in body shape and vertebra,（,deleted 6 pictures,）,normal,50,yrs,above 55yrs,above 75yrs,kyphosis,5,Patients with risk factors or conditions that cause osteoporosis,Postmenopausal woman with family history of hip fractures or kyphosis,Medications: corticosteroids, dilantin, gonadotropin releasing hormone agonists, loop diuretics, methotrexate, thyroid, heparin, cyclosporin, depot-medroxyprogesterone acetate,Hereditary skeletal diseases: osteogenesis imperfecta, rickets, hypophosphatasia,Endocrine and metabolic: hypogonadism, hyperparathyroidism, hyperthyroidism, Cushing syndrome, acidosis, Gauchers disease,Marrow diseases: myeloma, mastocytosis, thalassemia,Others: Anorexia, Malabsorption, Cystic fibrosis, Renal insufficiency, Hypercalciuria, Hepatic disease, Depression, Spinal cord injury, Systemic Lupus, Weight below healthy range, Cigarette smoking,6,Epidemiology,The population of older men and women has been increasing, and therefore the number of people with osteoporosis is increasing.,In the USA, about 21% of postmenopausal women have osteoporosis (low bone density), and about 16% have had a fracture. In women older than 80, about 40% have experienced a fracture of the hip, vertebra, arm, or pelvis.,Women have more osteoporotic fractures than men. Age is one of the most important risks in all groups.,The decreased physical activity may be playing a role in increased hip fractures.,7,Mechanism :,Bone physiology,The bone is continuously remodelling, and the bone surface moves in and out. The Basic Multicellular Unit (BMU) is a wandering team of cells that dissolves an area of the bone surface and then fills it with new bone. The sequence is Origination, Osteoclast recruitment, Resorption, Osteoblast recruitment, Osteoid formation,Mineralization,Mineral maturation, Quiescence.,Bone strength (Quality):,In addition to bone porosity, the bone strength is determined by the trabecular microstructure. Perforations of individual trabecula occur when resorption cavities are too deep. This, too, is seen with estrogen deficiency. The remaining trabecula are not as well connected and are mechanically weaker.,8,Mechanism :,Bone physiology,Microfracture healing is another aspect of bone strength that is not measured by bone density. Trabeculae inside the bone may fracture and microcalluses are formed that resemble the calluses seen on xrays of long bones after a macro-fracture. Osteoporotic bone is more susceptible to these fractures because the individual trabeculae do not have as many reinforcing connections. The calluses may represent a method of repairing the bone and even connecting some of the trabecula. Bone which has lost the ability to form these calluses will be weaker.,The age of the bone mineral crystals may also play a role in the strength of bone. This is an area that needs further research. Studies suggest that older bone is more brittle, and that one purpose of bone remodelling is to remove the old bone and replace it with newer, more elastic bone.,9,Clinical manifestation and types,Secondary osteoporosis,：,Mndocrine and metabolic: hypogonadism, hyperparathyroidism, hyperthyroidism, Cushing syndrome, acidosis, Gauchers disease;,Marrow diseases: myeloma, mastocytosis, thalassemia;,Medications: corticosteroids, dilantin, gonadotropin releasing hormone agonists, loop diuretics, methotrexate, thyroid, heparin, cyclosporin, depot-medroxyprogesterone acetate;,Malabsorption,、,Hepatic disease, others,；,Hereditary skeletal diseases:,osteogenesis imperfecta, rickets, hypophosphatasia;,Primary osteoporosis.,10,Clinical manifestation and types,Primary osteoporosis,：,Typepostmenopausal osteoroposis,This is seen with estrogen deficiency. There is high,bone turnover rate.,The proportion of trochanteric and femoral neck fractures increases,；,Type,elderly osteoroposis,This is aging in bone physiology. The compression fracture of the spine and hip fracture are more common.,11,Clinical Features of Osteoroposis,The vast majority of hip fractures occur after a fall. About 5% appear to be “spontaneous” fractures, in which the patient feels a fracture and then falls.,Overall about half of hip fractures are intertrochanteric and the others are femoral neck fractures.,12,Clinical Features of Osteoroposis,Vertebral compression fractures vary in degree from mild wedges to complete compression. The symptoms also vary, but the degree of compression is not necessarily related to the amount of pain. In fact,about 60% of women with compression fractures do not realize they have had a fracture!,It is possible that some of the fractures occurred gradually and therefore did not cause acute pain.,13,Clinical Features of Osteoroposis,When women and men do suffer painful compression fractures, the pain usually lasts from one to two months, is localized to the back with accompanying muscle spasms, then gradually subsides.,Patients with continuing severe pain should be evaluated for other pathologic etiologies of the fracture, especially malignancy or myeloma.,Persistent pain can also be caused by continuing fracture, muscle spasms, spinal stenosis, or degenerative joint disease.,14,Clinical Features of Osteoroposis,To correctly interpret a spine xray, it is important to know the,definition of a vertebral fracture, which is not quite as straightforward as it first appears, especially for research.,For practical clinical purposes, a vertebra can be considered fractured if the anterior height is 80% or less of the posterior height.,A new fracture requires loss of at least 20% of anterior or posterior height.,15,Clinical Features of Osteoroposis,Wrist fractures are more common in women who are 50 to 60 years old. These are caused by falls or other trauma. Osteoporosis does not appear to impair the healing of the wrist fractures, and they cause only short-term disability.,Although spine, hip, and wrist fractures are considered classical osteoporotic fractures, many others are related to bone density and thus are also osteoporotic. These include rib, pelvic and shoulder fractures, but not finger, facial bone, skull, elbow, or ankle fractures.,16,Clinical Features of Osteoroposis,The irreversible,height loss,associated with osteoporosis is one of the aspects of the disease that is most distressing to many women.,Height loss can also occur with scoliosis, which often gets worse after menopause.,Also, degenerative disk disease can cause height loss of 2 inches.,Some reversible height loss is due to poor posture.,KYPHOSIS,is the feature of osteoporosis that is identified by most patients. The hump causes difficulty in finding clothes that will fit, let alone look attractive. In severe cases, the ribs contact the iliac crest and movement causes pain.,17,Clinical Features of Osteoroposis,PROTRUDING ABDOMEN,The protruding abdomen which is a result of the kyphosis is an unrecognized aspect of osteoporosis. Women do not realize that the curvature of the spine decreases the abdominal space, and thus the intestines have nowhere to go except forwards. Many women think that they are getting fat, and they go on a diet trying to regain their youthful waistline. If they do successfully lose weight, it will only increase their risk for more osteoporotic fractures.,18,Clinical Features of Osteoroposis,DECREASED PULMONARY CAPACITY,Patients with kyphosis have decreased lung volumes. In severe cases this leads to shortness of breath and pulmonary symptoms of restrictive lung disease.,19,Clinical Features of Osteoroposis,REFLUX ESOPHAGITIS,Patients with kyphosis may develop reflux esophagitis due to the changes in abdominal space. Wearing tight clothing can exacerbate the problem.,20,Laboratory tests,For an uncomplicated patient with osteoporosis, a lab workup would be a chemistry panel, CBC, phosphate, TSH and 24-hour urine calcium. Males should have testosterone measured.,The main purpose of laboratory tests is to check for,secondary,causes of osteoporosis such as cases of renal or hepatic failure, anemia, acidosis, hypercalciuria, and abnormalities of calcium/phosphate.,21,Laboratory tests,Alkaline phosphatase is an inexpensive method of checking for osteoblastic activity. It is not as sensitive or specific as newer bone markers but it will detect moderate to severe osteomalacia or Pagets disease.,The 24-hour urine calcium measurement is frequently ignored but it is a valuable and inexpensive test. High levels are seen in idiopathic hypercalciuria, and low levels suggest malabsorption.,22,Laboratory tests,Protein electrophoresis should be done whenever a patient presents with new fractures. Both serum and urine tests should be done because some patients with myeloma have abnormalities in only one.,Corticosteroid excess that causes osteoporosis can usually be detected clinically by Cushingoid features. A urine cortisol can be helpful in puzzling cases.,23,Laboratory tests,Gonadal hormones are very important causes of osteoporosis. In females who are postmenopausal, it is not helpful to measure levels of estrogens or gonadotropins. In males, however, testosterone levels should be measured because there is much greater variability in the prevalence of hypogonadism. Also, men may have low testosterone without other clinical symptoms.,24,Laboratory tests,Vitamin D and parathyroid hormone levels are expensive tests. Mild vitamin D deficiency frequently occurs in the absence of hypocalcemia, but if vitamin D supplementation is routinely given, it is not necessary to perform this test in patients with normal calcium. Primary hyperparathyroidism nearly always causes hypercalcemia. Secondary hyperparathyroidism may occur with normal calcium, but most of these cases will be detected by low urine calcium or decreased renal function.,In patients with abnormal serum calcium or with unusually severe bone disease, however, the 25-OH-vitamin D and parathyroid hormone levels should be measured.,The 25 OH-vitamin D is more useful than the 1,25 (OH)2 vitamin D level.,25,Indications for bone density measurements,Over the last decade there have been many debates about screening bone density. Several organizations have performed detailed cost-benefit studies and developed guidelines; these must be continually revised as new findings about treatment effects are discovered.,Bone density tests carry no physical risks, but there is a problem of over-interpretation of results, so that healthy ordinary average people think they are at a much higher risk than they actually are.,26,Bone density measurements,Techniques,Several methods are available to measure bone density, but currently the most widely used technique is DEXA (Dual Energy Xray Absorptiometry). This is the method used to determine efficacy in the recent large clinical trials, and to characterize fracture risk in large epidemiological studies.,Newer techniques such as,ultrasound,appear to offer a more cost-effective method of screening bone mass. Ultrasound measurements are usually performed at the calcaneous and it is not possible to measure sites of osteoporotic fracture such as the hip or spine.,27,Bone density measurements,Quantitative computed tomography of the spine must be done following strict protocols in laboratories that do these tests frequently; in community settings the reproducibility is poor. The QCT measurements decrease more rapidly with aging, so the T scores in older individuals will be much lower than DEXA measurements.,Several other techniques can measure bone density at the hand, radius or ankle. These include single energy absorptiometry, metacarpal width or density from hand xrays. Magnetic resonance imaging is a new method of measuring bone density.,28,T & Z scores and the WHO definitions,The WHO has based definitions on the,T-score,which is the number of standard deviations from the mean (average) value of a 25-year-old woman.,Normal bone: T-score better than -1.,Osteopenia,: T-score between -1 and -2.5,Osteoporosis: T-score less than -2.5,Established osteoporosis,includes the presence of a non-traumatic fracture.,One standard deviation is at the 16th percentile, so by definition 16% of young women have,osteopenia,!,The,Z-score,is the number of standard deviations below age-matched,avereage,.,29,Bone density measurements,DEXA reports,Step 1: the images,Step 2 - the graphs,Step 3 - the basic results,Step 4 - the reference ranges,Beware the shifting reference ranges! Comparing a recent scan to one done prior to about 1997.,Step 5 - the areas and mineral contents,30,Bone Mineral Apparent Density,BMAD is important when measuring bone density in children or in patients with short stature. Another term for this concept is volumetric bone density.,The DEXA technique analyzes the attenuation of xrays as they pass through an area of the body. The method cannot detect the depth of the bone which is being measured, and thus is actually an areal density in g/cm2 rather than a volumetric or Archemdean density in g/cm3. As bones grow, the volume increases at a faster rate than the area, so the areal bone density will increase even if the volumetric density remains stable.,31,Standardization of BMD and Reproducibility,The three manufacturers of DEXA equipment do not give STANDARDIZED RESULTS. The differences are clinically important, making it difficult to compare a measurement made from one machine to the other.,Studies frequently report reproducibility of DEXA between 1 and 2%. This is the average precision; the range is rarely reported. But repeat measurements may show as much as 7% difference.,32,Biochemical markers of bone cell activity,BIOCHEMICAL MARKERS OF BONE RESORPTION,NTX Aminoterminal cross-linking telopeptide of bone collagen Collagen-based,CTX Carboxyterminal cross-linking telopeptide of bone collagen Collagen-based,PYD Pyridinoline Collagen-based,DPD Free Lysyl-pyridinoline (deoxypyridinoline) Collagen-based,TRACP Tartrate-resistant acid phosphatase Secreted by osteoclasts,Hyp Hydroxy-proline (not very specific) Collagen-based,33,Biochemical markers of bone cell activity,BIOCHEMICAL MARKERS OF BONE FORMATION,Bone ALP, BAP Bone-specific alkaline phosphatase Secreted by osteoblasts,PICP,Procollagen type I C propeptide,Collagen-based,PINP,Procollagen type I N propeptide,Collagen-based,OC Osteocalcin (bone gla-protein) Secreted by osteoblasts,ALP Alkaline phosphatase (not very specific) Secreted by osteoblasts,34,Biochemical markers of bone cell activity,The biochemcial markers of bone formation and bone resorption are frequently called markers of bone turnover. It is better to remember specifically which process is being measured, because sometimes the bone formation and resorption are not linked (for example, in steroid-induced osteoporosis, bone formation is low but bone resorption is high).,These markers can NOT BE USED TO DIAGNOSE OSTEOPOROSIS! They help us understand the physiology of bone disease, especially in groups of patients or in clinical trials. For individual patients, the markers are of limited use and not recommended for screening or routine follow-up. They do provide information which can help decisions in complex cases.,35,Diagnosis of osteoroposis,(,T & Z scores and the WHO definitions),Differential diagnosis,Remember that not all fractures are osteoporotic.,The differential diagnosis of fractures includes:,Trauma, Pathologic fracture from neoplasm,Osteomalacia, Pagets disease, Infections (such as TB), Fibrous dysplasia, Peripheral neuropathy, March fractures from repetitive stress,Many of these may be diagnosed from radiographs, bone scans, or magnetic resonance imaging studies. Sometimes bone biopsies are necessary.,36,Diagnosis and differential diagnosis,Physical finding,Patients with decreased bone density usually have no specific abnormal physical findings. Those with vertebral compression fractures will have kyphosis, protruding abdomen and height loss. Back tenderness is usually only present after an acute fracture. Gait speed and grip strength are often reduced in patients who have or are about to have a hip fracture. Visual acuity should be checked in geriatric patients because it is a risk factor for falling.,Secondary,causes of osteoporosis may be associated with physical findings, such as nodular thyroid, hepatic enlargement, cushingoid features, skin rashes, jaundice, abnormal dentition, and findings of hypogonadism.,37,Diagnosis and differential diagnosis,Xray findings,Sometimes decreased bone density (demineralization) can be detected by xray, but bones can appear normal despite loss of 30% of bone mineral. On the other hand, bones in over-exposed films can appear demineralized when they arent.,Bone density,measurements are much more accurate than xrays in determining bone density.,The Singh index of the proximal femur correlates with bone density. The trabeculae of the femur are lost in sequence, depending on the physical stresses to the bone, so the remaining trabecular pattern indicates the severity of bone loss.,Fractures,are discussed in the clinical description page.,38,Break 10 minutes,39,Prevention and Treatment,Basic prevention,Calcium,Vitamin D,Exercise,Fall prevention,Nutrition and weight gain,Stop smoking,When to add medications,40,Prevention and Treatment,Calcium to treat and prevent osteoporosis,Recommendations,Calcium intake of 1 to 1.5 g/day,Calcium content of foods,Forms of calcium,and,Dietary factors,Some practical information about calcium,Mechanisms of action,It is probably through inhibition of PTH secretion and effects of the calcium receptor.,Studies relating calcium intake to bone density,A study of calcium in men and women older than 65 showed that dietary calcium and vitamin D supplementation moderately reduced bone loss and reduced the incidence of nonvertebral fractures.,Side effects,41,Prevention and Treatment,Vitamin D,metabolism,It is formed in the skin after exposure to ultraviolet radiation and also is absorbed from the diet. It is hydroxylated at the liver to 25-hydroxyvitamin D, and in the kidney to 1,25-dihydroxyvitamin D which is the active form.,levels,Measure 25(OH) vitamin D, not 1,25(OH)2 vitamin D,supplements,natural sunlight and fortification of dietary foods, particulary dairy products and some cereals.,Active Metabolites,Disorders of vitamin D,42,Prevention and Treatment,Exercise,Physical activity,I recommend walking for prevention of hip fractures. Back extension exercises and Tai Chi also are beneficial.,Interventions in premenopausal, postmenopausal and elderly,women,Physical therapy,Specific exercises,Skeletal response to mechanical forces,43,Prevention and Treatment,Fall Prevention,The risk factors for falls include:,use of sedatives, previous fall, cognitive impairment, visual impairment, lower-extremity disability, foot problems, gait abnormalities,At home, elderly or frail people should:,keep bathroom lights on, install grab bars, avoid loose rugs, remove clutter, keep wires behind furniture,gait tr