- 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