No abstract

Aplastic bone disease (ABD) is a common form of renal osteodystrophy and is characterized by a defect in bone matrix formation and mineralization without an increase in osteoid thickness. The prevalence and pathogenesis of ABD in predialysis patients is largely unknown. We prospectively studied 92 unselected predialysis patients with a creatinine clearance < 10 ml/min/1.73 m2 and a mean age of 45 +/- 2 years (61 M, 31 F). None of the study patients had received any form of vitamin D therapy, and CaCO3 was the primary phosphate binder. Aplastic bone disease was observed in 30 (32%) patients. Stainable bone aluminium surface was < 3% in all ABD patients. Patients with ABD were older (52 +/- 3 versus 42 +/- 2 years; P < 0.01) and had reduced serum intact PTH compared to non-ABD patients (199 +/- 25 versus 561 +/- 87 pg/ml; P < 0.001). Patients with diabetes mellitus showed lower PTH values (179 +/- 31 versus 432 +/- 62 pg/ml; P < 0.001) and a lower incidence of advanced hyperparathyroidism bone lesions (16% versus 46%; P < 0.05) than non-diabetic patients. However, diabetes was not clearly associated with low bone turnover disease (56% in diabetics versus 41% in non-diabetics; P = 0.1). A second bone biopsy was obtained in eleven ABD patients after a period of 16.6 +/- 2.2 months on maintenance dialysis with a dialysate calcium of 7 mg/dl. Bone histology was unchanged in 10 patients, and one evolved to mild hyperparathyroidism. Trabecular bone volume did not change (22.7 +/- 1.7 versus 20.7 +/- 1.7%), and the stainable bone aluminium surface remained < 3%.(ABSTRACT TRUNCATED AT 250 WORDS)

To evaluate a possible relationship between vitamin D levels and bone mineral density (BMD) and the prevalence of hypovitaminosis in a population of postmenopausal women from a rheumatologic outpatient clinic in Madrid, Spain, 171 postmenopausal women (aged 47-66 years) divided into two groups (osteoporotic and nonosteoporotic, according to WHO criteria) were studied between November and June. Liver and kidney function were normal in all subjects. Serum parathyroid hormone (PTH) and calcidiol levels were determined and bone densitometry carried out at the lumbar spine and hip level. PTH and calcidiol serum levels did not show any correlation. Serum PTH was inversely related to BMD at both hip and lumbar spine in the total group, and at the hip with calcidiol levels lower than 37 nmol/l. Calcidiol was directly related to hip BMD only when levels were lower than 37 nmol/l. Results of a stepwise multiple regression analysis showed that the single factor which affected BMD at the hip was calcidiol in the subgroup with serum calcidiol levels below 37 nmol/l, while in the subgroup with serum calcidiol levels above 37 nmol/l, the main factor affecting hip BMD was serum PTH. The prevalence of vitamin D deficiency at a cutoff of 37 nmol/l was 64%. In summary, calcidiol serum levels below 37 nmol/l seem to affect bone mass, regardless of the effect of PTH. Vitamin D deficiency is a frequent finding in the postmenopausal women who attend a rheumatology outpatient clinic in Madrid. Vitamin D supplementation should therefore be considered in this population during the winter season.

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.

The relationship between vitamin D and bone density was studied in 150 selected, mature (45-74), postmenopausal women with a lumbar spine Z score below 0. Vitamin D status was evaluated using calcidiol serum levels. Serum calcitriol and parathyroid hormone (PTH) values were also evaluated in some subjects. Bone mass was evaluated by ascertaining bone density and Z and T scores in the lumbar spine and femur region. The reference group consisted of 25 premenopausal women. The postmenopausal group was divided into subgroups according to age, i.e., under or over 60 years old. Additionally, the whole group was also subdivided according to their lumbar spine Z scores into group I (Z > -1), group II (Z < -1; > -2), and group III (Z < -2). Group III of postmenopausal women had higher PTH and lower calcitriol levels than premenopausal women. Calcidiol serum levels were lower in postmenopausal women groups II or III than in the group I and premenopausal women. Calcidiol serum levels and the bone mass values for the lumbar spine were correlated positively in all the postmenopausal women; in the women over 60 years of age, calcidiol levels also correlated with the bone mass values expressed as the bone density in three femur regions: femoral neck, trocanter, and Ward's triangle. In conclusion, mature post-menopausal woman showed high PTH levels and low calcidiol and calcitriol values. Calcidiol status is significantly related to bone mineral density in the lumbar spine and in women over 60 years, calcidiol levels also correlated with bone density in the femur regions.

We evaluated urinary excretion of free pyridinoline (PYD)-deoxypyridinoline (DPD) by an enzymelinked immunosorbent assay (ELISA) method, free and total PYD by high-performance liquid chromatography (HPLC), free DPD by ELISA, chemiluminiscent immunoassay (CLEIA) and HPLC, total DPD by HPLC, and N-telopeptides (NTX) and C-telopeptides (CTX) by ELISA in 234 women distributed into three groups: 43 healthy young women (aged 26.2 +/- 2.5 years), 56 control postmenopausal women (aged 55.9 +/- 4.5 years) and 133 untreated osteoporotic women (aged 55.1 +/- 4.0 years). The control postmenopausal women had increased values of all markers considered, except NTX, compared with healthy young women. The osteoporotic postmenopausal women had significantly increased values compared with control postmenopausal women for free DPD by HPLC and free DPD by ELISA or CLEIA. HPLC, ELISA and CLEIA showed adequate correlation to measure free PYD and DPD. Control postmenopausal women had significantly decreased values of the fraction of free PYD and DPD (48.4% and 32.0%, respectively), as did the osteoporotic postmenopausal women (48.0% and 46.1%), compared with healthy young women (55.3% and 57.0%). We found a significant negative correlation comparing age with fraction of free PYD and DPD, but a positive correlation with total PYD and DPD, considering or not the osteoporotic postmenopausal women. T-score and Z-score values derived from healthy young women and control postmenopausal women for PYD, DPD, NTX and CTX measured by immunoassays were calculated to detect changes in bone turnover, DPD by ELISA or CLEIA showing the highest Z-score. The sensitivity and specificity of the different assays were evaluated using a receiver operating characteristic (ROC) curve. With a specificity of 90% the sensitivity of the markers considered was low (from 33% for DPD by CLEIA to 11% for PYD-DPD by ELISA), but increased considerably with a specificity of 75%. In conclusion, urinary pyridinium crosslink derivatives increase with age and after the menopause, and rise slightly in women with osteoporosis, there being a negative correlation among age and the fraction of free PYD and DPD of the total urinary excretion. Among the resorption markers most often available in clinical laboratories, free DPD by ELISA or CLEIA was the best at discriminating osteoporotic postmenopausal women from aged-matched control postmenopausal women.

No abstract

The bisphosphonate alendronate is a potent inhibitor of bone resorption by its direct action on osteoclasts. In addition, there is some data suggesting that alendronate could also inhibit bone resorption indirectly by interacting with osteoblasts. Parathyroid hormone-related protein (PTHrP) produced by osteoblasts and 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] are regulators of bone remodeling, which have interrelated actions in these cells. In this study, we assessed whether alendronate can affect PTHrP expression in the presence or absence of 1,25(OH) 2 D 3 in human primary osteoblastic (hOB) cells from trabecular bone. Cell total RNA was isolated, and semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) was carried out using human PTHrPspecific primers. PTHrP in the hOB cell-conditioned medium was analyzed by a specific immunoradiometric assay. We found that PTHrP mRNA and secreted PTHrP were maximally inhibited by 10