Hormonal influences. In the decade after menopause, yearly reductions in bone mass may be as much as 2% of cortical bone and 9% of medullary bone. Estrogen deficiency plays the major role in this phenomenon and close to 40% of postmenopausal women are affected by osteoporosis. Decreased estrogen levels after menopause increase both bone resorption and formation but the latter does not keep up with the former, leading to high-turnover osteoporosis. The decreased estrogen may increase secretion of inflammatory cytokines by monocytes. These cytokines stimulate osteoclast recruitment and activity by increasing the levels of RANKL, diminishing the expression of OPG, decreasing osteoclast proliferation, and preventing osteoclast apoptosis. Cytokines such as IL-6, TNF-α, and IL-1 also have been implicated in postmenopausal osteoporosis, either independently or as downstream mediators of estrogen signaling.
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Fig.21.6Osteoporoticvertebralbody(right) shortenedbycompressionfracturescomparedwithanormalvertebralbody(left).Notethattheosteo-poroticvertebrahasacharacteristiclossofhorizontaltrabeculaeandthick-enedverticaltrabeculae.
MORPHOLOGYThehallmarkofosteoporosisishistologicallynormalbonethatisdecreasedinquantity.Theentireskeletonisaffectedinpostmenopausalandsenileosteoporosis,butcertainbonestendtobemoreseverelyimpacted.Inpostmenopausalosteoporosistheincreaseinosteoclastactivityaffectsmainlybonesorportionsofbonesthathaveincreasedsurfacearea,suchasthecancellouscompartmentofvertebralbodies(
Fig.
21.6 ).Thetrabecularplatesbecomeperforated,thinned,andlosetheirinterconnections(
Fig.21.7 ),leadingtoprogressivemicrofracturesandeventualvertebralcollapse.
The clinical manifestations of osteoporosis depend on which bones are involved. Vertebral fractures that frequently occur in the thoracic and lumbar regions are painful, and, when multiple, can cause significant loss of height and various deformities, including lumbar lordosis and kyphoscoliosis. The immobility following fractures of the femoral neck, pelvis, or spine results in complications such as pulmonary embolism and pneumonia, accounting for 40,000 to 50,000 deaths per year.
Fig.21.7Inadvancedosteoporosis,boththetrabecularboneofthemedulla(bottom) andthecorticalbone(top) aremarkedlythinned.
Osteoporosis cannot be reliably detected in plain radio-graphs until 30% to 40% of the bone mass is lost, and measurement of blood levels of calcium, phosphorus, and alkaline phosphatase are not diagnostic. Osteoporosis is thus a difficult condition to screen for in asymptomatic people. The best estimates of bone loss, aside from biopsy (which is rarely performed), are specialized radiographic imaging techniques, such as dual-energy x-ray absorptiometry and quantitative computed tomography, both of which measure bone density.