Bone loss with aging may be due, at least in part, to inadequate bone formation. Moreover, the process of bone aging is known to follow a different pattern throughout the skeleton. In this study, we examined the cell proliferation rate (area under the cell growth curve, AUC) and the secretion of C-terminal type I procollagen (PICP), alkaline phosphatase (ALP), and osteocalcin (OC) in primary cultures of osteoblastic cells from human trabecular bone. Osteoblastic cells were obtained for 168 donors (100 women and 68 men). Ninety-eight bone samples were obtained from subjects undergoing knee arthroplastia, 52 aged 50-70 years (64 +/- 5) and 46 over age 70 (73 +/- 2). Another 70 bone samples were obtained from subjects undergoing hip arthroplastia; 51 were 50-70 years old (64 +/- 4) and 19 were over 70 (75 +/- 5). Osteoblastic cells from the older donors had a lower proliferation rate and OC secretion than those from younger subjects. However, ALP secretion was higher in the former subjects, whereas PICP secretion was unchanged. Osteoblastic cells from hip had a lower proliferation rate than those from knee. PICP secretion was also lower and ALP secretion was higher in the former cells. In age-matched cell cultures, osteoblastic cells from the knee had higher proliferation rate and PICP secretion than osteoblastic cells from the hip. However, ALP secretion was lower in knee osteoblastic cells than those from hip only in the younger group. With aging, ALP secretion was found to increase in knee osteoblactic cells, whereas OC secretion decreased in osteoblastic cell cultures from the hip. Our findings suggest that bone loss with aging may be accounted for, at least in part, by a decreased osteoblastic cell proliferation and an increased osteoblastic maturation. In addition, our data indicate that these changes with aging do not occur similarly at different skeletal sites.

Osteogenesis and angiogenesis occur in a coordinated manner in skeletal tissue, so that impaired angiogenesis is associated with decreased bone formation in aged subjects. However, the interaction between bone endothelium and osteoblastic cells is poorly understood. Parathyroid hormone-related protein (PTHrP), a bone factor which modulates osteoblastic cell growth and/or differentiation, stimulates vascular endothelial growth factor (VEGF), a potent angiogenic factor, in primary cultures of human osteoblastic (hOB) cells. In the present study, we examined the age-related changes of both factors in these cells. Human OB cells were isolated from trabecular bone samples from knee or hip explants obtained from 45 osteoarthritic patients: 12 <60 years (21-59 years), 5 women and 7 men, and 33 >60 years (61-82 years), 20 women and 13 men. Cell total RNA was isolated, and mRNA analysis was performed by reverse transcription-polymerase chain reaction. Relative ratios of amplified products with respect to glyceraldehyde-3-phosphate dehydrogenase were then calculated. PTHrP and VEGF were measured in the cell-conditioned medium, after stimulation with (or without) 10 nM 1,25(OH)(2)D(3) for 72 h, using specific immunoradiometric assay and a competitive immunoassay, respectively. A positive correlation was found between PTHrP and VEGF (both mRNA and secreted protein), and also between PTHrP mRNA and the secreted protein levels, in these cells. PTHrP, both mRNA and protein secretion levels, and VEGF secreted values were higher in knee hOB cells than in hip hOB cells only in the younger group. In addition, a decrease in the secreted levels of these factors occurs with aging only in hOB cells from knee. Treatment with 10 nM 1,25(OH)(2)D(3) induced a lower inhibitory response of PTHrP secretion, and a higher stimulatory response of secreted VEGF, in hOB cells with age. These findings indicate that age-related bone loss in humans is associated with a decrease in the osteoblastic secretion of both PTHrP and VEGF in the knee, a predominantly trabecular bone. These data might provide a rationale to explain the impaired angiogenesis associated with trabecular bone loss in aging.

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Gout is commonly associated with obesity, arterial hypertension, diabetes, and dyslipidemia. However, the prevalence of metabolic syndrome has not been widely recognized in patients with gout. We studied 41 patients (37 males) with primary gout to assess the prevalence and characteristics of the associated metabolic syndrome. Twenty-one patients with gout (51%) showed >or=3 criteria for the metabolic syndrome. Pathological conditions associated were obesity (21/41), high blood pressure (30/41), dyslipidemia (30/41), and fasting plasma glucose >or= 100 mg/dL (22/41). The most frequent triad was the presence of increased waist circumference, elevated fasting plasma glucose, and hypertension. Mean serum urate concentration did not differ significantly in gout patients with the metabolic syndrome (8.5 mg/dl) and without (8.1 mg/dl). Given the complications associated with metabolic syndrome, its diagnosis may determine the long-term treatment of patients with gout.