Osteoporosis in hemodialysis patients revisited by bone histomorphometry: a new insight into an old problem.
Osteoporosis in hemodialysis patients is associated with high morbidity and mortality and, although extensively studied by noninvasive methods, has never been assessed through bone biopsy. The aim of this study was to use histomorphometry to evaluate osteoporosis and identify factors related to its development in hemodialysis patients. We conducted a cross-sectional study involving 98 patients (35 women and 63 men; mean age: 48.4 +/- 13 years) on hemodialysis for 36.9 +/- 24.7 months. Patients were submitted to transiliac bone biopsy with double tetracycline labeling. The bone metabolism factors ionized calcium, phosphorus, bone alkaline phosphatase, deoxypyridinoline, intact parathyroid hormone, and 25(OH) vitamin D were evaluated, as were the bone remodeling cytokines osteoprotegerin (OPG), soluble receptor-activator of NF-kappabeta ligand (sRANKL) and tumor necrosis factor-alpha (TNF)alpha. Osteoporosis was defined as trabecular bone volume (BV/TV) greater than 1 s.d. below normal (men <17.4%; women <14.7%). Forty-five patients (46%) presented osteoporosis, which was correlated with white race. We found BV/TV to correlate with age, OPG/sRANKL ratio, TNFalpha levels, and length of amenorrhea. In multiple regression analysis adjusted for sex and age, length of amenorrhea, white race, and OPG/sRANKL ratio were independent determinants of BV/TV. Histomorphometric analysis demonstrated that osteoporotic patients presented normal eroded surface and low bone formation rate (BFR/BS). Osteoporosis is prevalent in hemodialysis patients. Low BFR/BS could be involved in its development, even when bone resorption is normal. Cytokines may also play a role as may traditional risk factors such as advanced age, hypogonadism, and white race.
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Department of Internal Medicine, Division of Nephrology, Federal University of São Paulo, Brazil. fellype.barreto@terra.com.br
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D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D000596:Amino Acids / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D001851:Bone Diseases, Metabolic / Q000473:pathology*; D016723:Bone Remodeling; D001842:Bone and Bones / Q000473:pathology*; D002118:Calcium / Q000097:blood; D002352:Carrier Proteins / Q000097:blood; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D008875:Middle Aged; D010024:Osteoporosis / Q000097:blood / Q000453:epidemiology / Q000378:metabolism* / Q000503:physiopathology; D053244:Osteoprotegerin; D010281:Parathyroid Hormone / Q000097:blood; D010758:Phosphorus / Q000097:blood; D015995:Prevalence; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D006435:Renal Dialysis / Q000009:adverse effects*; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood; D044465:White People / Q000706:statistics & numerical data
D000596:Amino Acids; D015415:Biomarkers; D002352:Carrier Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D010281:Parathyroid Hormone; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D014807:Vitamin D; D010758:Phosphorus; C036020:deoxypyridinoline; C104450:25-hydroxyvitamin D; D000469:Alkaline Phosphatase; D002118:Calcium