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Osteoporosis

- Discussion:                                                                                                          
    - most common metabolic bone dz
    - definition:
           - what appears to be a characteristic of osteoporosis is an uncoupling of the osteoblastic and osteoclastic processes;
           - WHO definition: a bone mineral density that is 2.5 SD below the mean peak value in young adults of the same race and sex (T-score of -2.5);
           - Z score: bone mineral density compared w/ mean value in normal subjects of same age and sex; 
           - Z-score of less than -1 indicates patient is in lowest 25%, and score of less than -2 indicates patient is in lowest 2.5%;
    - bone turnover and bone loss in adults:
           - approx 3 % of cortical bone is replaced each year;
           - approx 25 % of trabecular bone is resorbed & replaced every year;
                  - trabecular bone has high surface-to-volume ratio, & 70-85 % of surface of the bone is in contact with bone marrow;
           - after the mid thirties, there is 0.3 to 0.5 % bone loss per year;
           - total bone loss in osteoporosis may exceed 30 to 40%;
           - in early osteoporosis, there will be bone loss of 2-3 % per year (majority occurs in cancellous bone), but this rapid loss may decrease after 6-10 years;
    - risk of fracture:
           - 40% of 50 year old females will have an osteoporotic fracture during their lifetime; 
           - in women there is a 15-18% lifetime risk of hip fracture after age 50 yrs, vs 6% risk in men; 
                 - Lifetime absolute risk of hip and other osteoporotic fracture in Belgian women.
                 - Lifetime risk of hip fractures is underestimated.
                 - Contralateral hip fractures and other osteoporosis-related fractures in hip fracture patients: incidence and risk factors. An observational cohort study of 1,229 patients 
           - vertebral body fractures 
    - classfication:
           - type I ("postmenopausal") osteoporosis
           - type II ("senile") osteoporosis
           - secondary osteoporosis:
                   - laboratory studies:
                         - liver function tests and levels of calcium, albumin, 25-hydroxyvitamin D, intact PTH, and thyroid-stimulating hormone in all patients and a total serum testosterone level in men;
    - histology:
           - bone is normal, but there is too little of it;
           - bone that is present is lamellar in character and w/o osteoid seams, resorption cavities, or osteoblastic or osteoclastic activity.
    - specific causes and differential dx of osteoporosis:
           - etiology is multifactorial; 
    - references:
           - Bona Fide Genetic Associations with Bone Mineral Density
           - Multiple Genetic Loci for Bone Mineral Density and Fractures

 


- Methods to Quantify Osteoporosis:
    - generally osteoporosis is quantified as a percentage of a standard deviation below normal (compared to age matched controls);
           - one standard deviation below normal is mild to moderate where as two standard deviations below normal implies severe osteoporosis;
    - dual X-ray absorptiometry (Dexa) (preferred technique)
    - dual photon absorptiometry
    - single photon absorptiometry:
    - quantitative CT:
    - Singh index:


- Treatment:
    - first important task is to r/o hyperthyroidism because it represents only truly reversible form of the disease;
           - be sure that patients taking synthroid are not over-medicated;
    - spine in osteoporosis:
    - hip in osteoporosis:
    - younger women: (premenopause)
             - check a thyroid panel since hyperthryoidism is the only reversible form of osteoporosis;
             - normal menstration:
                   - calcium: 500 mg of calcium carbonate to be taken orally three times a day;
                   - Vit D: 800 units of vitamin D3 PO qd (after determining that the serum Ca is not elevated);
             - amenorrhea
                   - menstrual irregularity is often associated w/ stress frxs in female runners.
                   - estrogen has protective effects against osteoporosis;
                   - female runners who have used birth control pills for over 1 year have a lower rate of stress frxs than women who have not used birth control pills;
    - type I (postmenopausal osteoporosis)
    - type II ("senile" osteoporosis)
           - elderly women or men w/ frx of hip & other bones caused by osteoporosis have already lost most of bone they will ever lose;
           - estrogen:
                  - there is no convincing evidence that estrogen benefits women over age of 75 years;


- Treatment Agents:
    - vit D:
              - vit-D and calcium supplements will prevent some degree of loss of skeleton and decrease likelihood of frx;
              - 800 units of vitamin D3 PO qd (after determining that the serum Ca is not elevated);
              - reference:
                   - Calcium plus Vitamin D Supplementation and the Risk of Fractures.
    - estrogen:
              - calcium, estrogen, & calcitonin act by decreasing bone resorption;
              - calcium & estrogen act mainly by decreasing activation of new bone remodeling units (not by decreasing action of existing osteoclasts);
              - estrogen may counteract effect of parathyroid hormone on bone;
              - action may be indirect since bone cells apparently lack estrogen receptors;
              - when estrogen cannot be taken due to concerns about breast cancer, then consider tamoxifen (nolvadex);
                     - this is almost as effect as estrogen and is used in the treatment of breast cancer; 
    - Forteo
    - raloxifene (evista):
              - selective estrogen receptor agonist that activates estrogen receptors in bone tissue and inhibits bone resorption w/o stimulating the uterine endometrium;
    - calcium:
              - calcium, estrogen, & calcitonin act by decreasing bone resorption;
              - calcium & estrogen act mainly by decr activation of new bone-remodeling units (not by decr action of existing osteoclasts);
              - national research council's RDA of calcium is 800 mg/day.
              - calcium metabolic balance studies indicate that premenopausal & estrogen-treated women require approx 1,000 mg of calcium / day;
              - dose: 500 mg of calcium carbonate to be taken orally three times a day;
              - postmenopausal women who are not treated w/ estrogen require about 1,500 mg daily for calcium balance;
              - high dietary calcium suppresses age-related bone loss and reduces fracture rate in patients w/ osteoporosis.
              - reference:
                   - Calcium plus Vitamin D Supplementation and the Risk of Fractures.
    - calcitonin
              - calcium, estrogen, & calcitonin act by decreasing bone resorption.
              - calcitonin may act directly on osteoclasts, which do have calcitonin receptors.
              - calcitonin has recently been shown to be an effective agent in management of patients with osteoporosis, although the drug is expensive and difficult to administer;
              - use of drug in inhalant form may make it a more feasible option.
    - biphosphonates:
              - fosamax (alendronate): first line agent;
              - etidronate
    - sodium fluoride



- Outside Links:
 
     
   

    osteoporosis and bone physiology at Washington University



- References for Osteoporosis
- Patient's Guide to Osteoporosis



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