Measurement of osteocalcin.
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Bone and Bones↗
Biomedical subjects
R Eastell
Publications and source records attributed to R Eastell.
The role of insulin-like growth factor I in age-related changes in calcium homeostasis in men.
The aim of this study was to evaluate hormonal influences on age-related changes in calcium homeostasis in men. We recruited 178 healthy men, ages 20-79 (about 30 per decade). We measured serum calcium, phosphate, urinary calcium, and creatinine clearance. Dietary calcium intake and use of fish oils were determined by questionnaire. Fractional calcium absorption was estimated using the stable strontium technique in a subgroup of 60 men. PTH, 1, 25-dihydroxyvitamin D [1,25(OH)(2)D], 25-hydroxyvitamin D (25OHD), serum insulin-like growth factor I (IGF-I), and testosterone were measured in all men. There was no change in serum calcium with age. There were decreases in serum phosphate, urinary calcium, and creatinine clearance with age (P: < 0.02). Dietary calcium was unchanged. Strontium absorption decreased (P: < 0.01), and PTH increased (P: < 0.001) with age. The data for 1,25OH(2)D were biphasic, reaching a peak at age 55 yr (P: = 0.003). There was a linear increase in 25OHD with age (P: = 0.009) that persisted after correcting for seasonal variation and was positively associated with fish oil use, therefore, the age-related changes in 25OHD were masked by self medication. There were log-linear decreases in IGF-I and testosterone with age (P: < 0.0001). Strontium absorption was not related to 25OHD or 1,25(OH)(2)D, but was positively correlated with IGF-I. 1,25(OH)(2)D correlated negatively with serum phosphate and calcium, but not PTH or creatinine clearance. IGF-I was positively associated with creatinine clearance, serum calcium, and phosphate and negatively associated with PTH (P: < 0.001). In this cross-sectional study of otherwise healthy, normally aging men, age-related decreases in IGF-I seem to have a greater impact on mineral absorption than does vitamin D status.
Adult↗
The effect of pregnancy on bone density and bone turnover.
During pregnancy, the mother adapts to meet the calcium demands of the fetus. The effect of this adaptation on the maternal skeleton is not fully understood. Our objectives were to evaluate changes in bone mineral density (BMD) and bone turnover during pregnancy. We studied 16 women longitudinally, with baseline measurements before pregnancy; then at 16, 26, and 36 weeks of pregnancy; and postpartum. We measured total-body BMD and biochemical markers of bone resorption (urinary pyridinium crosslinks and telopeptides of type I collagen) and bone formation (serum bone alkaline phosphatase, propeptides of type I procollagen [PINP] and osteocalcin). We also measured parathyroid hormone (PTH), insulin-like growth factor I (IGF-I), and human placental lactogen. Postpartum, BMD increased in the arms (2.8%, P < 0.01) and legs (1.9%, P < 0.01) but decreased in the pelvis (-3.2%, P < 0.05) and spine (-4.6%, P < 0.01) compared with prepregnancy values. All biochemical markers, with the exception of osteocalcin concentration, increased during pregnancy. The change in IGF-I at 36 weeks was related to the change in biochemical markers (e.g., PINP, r = 0.72, P = 0.002). Pregnancy is a high-bone-turnover state. IGF-I levels may be an important determinant of bone turnover during pregnancy. Elevated bone turnover may explain trabecular bone loss during pregnancy.
Adult↗
Identification of vertebral deformities in women: comparison of radiological assessment and quantitative morphometry using morphometric radiography and morphometric X-ray absorptiometry.
Our aim was to compare normal vertebral reference values for morphometric radiography (MRX) and morphometric X-ray absorptiometry (MXA) and to compare these methods for the identification of vertebral deformities. We calculated MXA reference values (Hologic QDR 4500 A) for 327 women (ages 22-88 years) randomly selected from local General Practice lists in Sheffield, U.K. MRX reference values were calculated from spinal radiographs for 123 of these subjects (ages 56-88 years). We used these reference values to identify deformities in the MRX and MXA reference populations and in 83 women with osteoporosis (ages 49-87 years). We observed differences in mean deformity of vertebral height ratios measured by MRX and MXA, especially for the mid-to-posterior ratio. We compared agreement between quantitative methods (MRX and MXA) and qualitative radiological assessment. Severity of deformity was defined by semiquantitative (SQ) assessment. Agreement was moderate for MRX (k = 0.59; 95% CI = 0.43-0.77) and for MXA (k = 0.47; 95% CI = 0.29-0.66) in the reference population. Agreement was good for MRX (k = 0.86; 95% CI = 0.82-0.89) and MXA (k = 0.71; 95% CI = 0.66-0.75) in the osteoporotic population. MRX and MXA correctly identified a greater proportion of moderate or severe deformities compared with mild deformities. Sensitivity, specificity, predictive values, and accuracy were slightly better for MRX than for MXA. Although MXA agrees well with qualitative radiological assessment, the large proportion of vertebrae excluded from analysis because of poor image quality limits the diagnostic value of the technique. Reference intervals should be technique specific.
Absorptiometry, Photon↗
Biological variability of serum and urinary N-telopeptides of type I collagen in postmenopausal women.
Measurement of N-telopeptides of type I bone collagen (NTX) provides a specific indicator of the current level of bone resorption. The biological intrasubject variability of NTX in urine and serum was studied in 277 postmenopausal women, mean age, 63.6 years +/- 10.2 (+/-SD) years. Second-morning void urine and serum specimens were collected at baseline and for two consecutive days to determine short-term variability (% CV). Long-term variability was determined by comparing NTX results at baseline and two consecutive months. Subjects were instructed to maintain current diet, lifestyle, and medications during the study. The median short-term %CV was 13.1% for urine NTX. This compared with 6.3% for serum NTX. Calculation of long-term %CV showed similar trends, with the %CV for NTX measured in serum (7.5%) lower than when measured in urine (15.6%). Using the least significant change (LSC) calculation, our data show that to be 90% confident that a decrease in NTX after initiation of antiresorptive therapy in an individual patient is not caused by variability alone, a 31 % decrease in urine NTX and a 14% decrease in serum NTX is required. As reported changes in NTX caused by antiresorptive therapy are greater than these calculations; our results support the use of either specimen to measure NTX to monitor the effect of therapy.
Aged↗
Biochemical markers as predictors of rates of bone loss after menopause.
Biochemical markers of bone turnover may correlate with rates of bone loss in a group of postmenopausal women, but it is uncertain how useful they are in predicting rates of bone loss in the individual. The aim of this study was to determine the value of measurements of biochemical markers for the prediction of rates of bone loss in the individual. We studied 60 postmenopausal women (ages, 49-62 years), 43 of whom had gone through a natural menopause 1-20 years previously and 17 of whom had undergone hysterectomy 3-22 years ago. Lumbar spine bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DXA) over 2-4 years. Bone formation markers (bone-specific alkaline phosphatase [ibAP] and amino terminal of type I collagen [PINP] and osteocalcin [OC]) were measured in serum. Bone resorption markers (N-telopeptide of type 1 collagen [NTx] and immunoreactive free deoxypyridinoline [iFDpd]) were measured in urine and corrected for creatinine (Cr). Rates of bone loss were calculated as percent change per year. We found significant negative correlations (Spearman rank) between all measured biochemical markers and rate of change in bone density with r values ranging from -0.35 to -0.52. When markers and rates of bone loss were divided into tertiles, prediction of bone loss in an individual was poor (kappa < 0.2). There was an exponential relationship between rate of bone loss and years since menopause (YSM) in the 43 women having a natural menopause (r2 = 0.44; p = 0.008) indicating higher rates of loss in the early postmenopausal period. Levels of NTx, iFDpd, and PINP also showed a significant negative correlation with YSM. We conclude that there is a strong relationship between rates of spinal bone loss and levels of bone turnover markers. Although this is a small study, the results also suggest that using DXA measurements of the lumbar spine as the "gold standard," it is not possible to use biochemical markers to predict rate of bone loss in the individual.
Absorptiometry, Photon↗
Immediate changes in biochemical markers of bone turnover and circulating interleukin-6 after parathyroidectomy for primary hyperparathyroidism.
OBJECTIVE: The time course of the immediate change in bone turnover after parathyroidectomy (PTX) for primary hyperparathyroidism (PHPT) is not clear. It is uncertain whether circulating interleukin-6 (IL-6) plays a role in mediating the acute withdrawal of the effects of parathyroid hormone (PTH) on bone turnover after PTX. The aims of this study were to determine the time course of immediate changes in biochemical markers of bone turnover after PTX and whether circulating IL-6 is involved in the immediate changes of bone turnover after PTX. DESIGN AND METHODS: IL-6 and bone turnover markers were measured in eight women (aged 55+/-11 years, mean+/-s.d. ) with PHTP at baseline and at 1-2h, and 1, 2, 5, 7 and 12 days after PTX. We compared the results with those from eight individually matched women (healthy controls) and five subjects undergoing major surgery (surgical controls). RESULTS: At baseline, serum levels of IL-6 and bone turnover markers were higher in PHPT than those in healthy controls (P<0.05). Serum levels of procollagen propeptides increased by 22 and 27% at days 2 and 5, respectively, compared with baseline (P<0.05). Serum tartrate-resistant acid phosphatase decreased by 2 days after PTX, and urinary collagen crosslinks decreased significantly by 21-41% within 24h (P<0.05). Serum IL-6 levels increased immediately in both PHPT and surgical controls at postoperative follow-up (repeated measures ANOVA). CONCLUSIONS: (1) PTX decreases bone resorption immediately and (2) circulating IL-6 is not involved in the changes in bone turnover immediately after PTX.
Adult↗
Zinc supplementation and bone growth in pubertal girls.
We supplemented the diets of 47 peripubertal girls with zinc (15 mg/day) or placebo for 6 weeks. Zinc supplementation increased serum zinc. Insulin-like growth factor I and biochemical markers of bone turnover did not change, albeit dietary zinc was below the reference level (in 94% of individuals).
Adolescent↗
Commentary: bone density can be used to assess fracture risk.
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Bone Density↗
Total body and regional bone mineral density in men: effect of age.
Bone density is related to the risk of fracture, with a decrease in bone density resulting in an increased risk of fracture. The aims of this study were to characterize the relationship between bone mineral density (BMD) and age at different skeletal sites in men, and to determine whether the BMD pattern with age reflects the pattern of fracture in men. We studied 178 healthy Caucasian men, ages 20-79 years (approximately 30 per decade) from a general practitioner register. Spinal radiographs were obtained from men over 50 years of age and graded by a radiologist for spinal osteoarthritis by the method of Kellgren. BMD was measured by dual-energy X-ray absorptiometry at the anteroposterior (AP) lumbar spine, femoral neck, Ward's triangle, trochanter, ultradistal forearm and total body (providing estimates for the pelvis, head, arms, legs, trunk, ribs and spine). Severe osteoarthritis (grades 3 and 4) was associated with increased spine BMD, and therefore individuals with severe osteoarthritis were excluded from analysis of the spine. There was a decrease in height of vertebrae L2-4 in men between 20 and 79 years of age (4%), resulting in a decrease in projected area. The change in BMD in standard deviation units (T-score) between 20 and 79 years was calculated: there were significant decreases at the femoral neck (-1.6), Ward's triangle (-2.4), total body (-0.6), and its subregions the pelvis (-1.4), trunk (-0.8), ribs (-0.7) and legs (-0.7). There was no change in BMD with age at the AP lumbar spine, ultradistal forearm, or the total body subregion of the head. Similar results were found after adjusting for height and weight. Thus, there was only a small decrease in total body BMD across life, but a substantial decrease in BMD of the pelvis and proximal femur, sites rich in trabecular bone. These are the same sites associated with substantial increases in fracture incidence in men with aging.
Adult↗
Identification of vertebral deformities in men: comparison of morphometric radiography and morphometric X-ray absorptiometry.
Osteoporotic vertebral deformities may be detected by morphometric radiography (MR) using spinal radiographs, and by morphometric X-ray absorptiometry (MXA) using dual-energy X-ray absorptiometry. Reference values for MR may not be appropriate for MXA, and reference values may be affected by gender and age. The aims of this study were to (1) compare mean deformity of vertebral height ratios for MR and MXA in men, (2) compare mean deformity for MXA in men and women, (3) compare mean wedge angle measured by MXA in men and women and (4) assess the effect of aging on MXA values in men. We studied a general practitioner sample of 115 men aged 22-81 years (mean 53 years) and 124 women aged 55-89 years (mean 68 years). Subjects had MXA of T4 to L4 using the Hologic QDR 4500A. Women and men over age 50 years had radiographs of the thoraco-lumbar spine. Scans and radiographs were marked in the same way by one operator and vertebral height ratios and mean deformity were calculated for MR and MXA. The mean wedge angle, θ, was calculated for MXA in all subjects. Mean wedge and biconcavity deformity and standard deviation (SD) in men were greater for MXA than for MR. The mean wedge and biconcavity deformity measured by MXA tended to be greater for men than for women. Vertebral deformity in men increased with age, and was associated with degenerative change seen on spinal radiographs. The mean wedge angle was greater for men than for women, and it increased with age in men. We conclude that sex- and age-specific reference ranges should be established separately for MXA.
Absorptiometry, Photon↗
Determinants of bone loss in elderly men and women: a prospective population-based study.
While several studies have described the rate and pattern of involutional bone loss in women, far less information is available for men. Furthermore, the roles of lifestyle and body build in determining bone loss rate in both sexes have been largely extrapolated from cross-sectional studies. We addressed this issue in a population-based longitudinal study which sought to ascertain rates of bone loss at the femoral neck and lumbar spine in a cohort of men and women aged 60-75 years at baseline, and to relate this loss to anthropometric and lifestyle variables. We additionally investigated the capacity of biochemical markers of bone turnover to predict bone loss rates in these subjects. Women lost bone at all sites; this ranged from 0.20%/year at the lumbar spine to 1.43%/year at the femoral trochanteric region. By contrast, men lost only 0. 20%/year at the trochanteric region, and gained at the lumbar spine (0.33%/year) and at Ward's triangle (0.27%/year) over the 4-year period. Anthropometric measurements were associated with bone loss in both sexes; lower baseline body mass index (BMI) and a greater rate of loss of adiposity over the follow-up period were both associated with greater bone loss at all proximal femoral sites. These attained statistical significance after Bonferroni correction at the total proximal femur among both men (r = 0.29), p<0.01) and women (r = 0.31, p<0.05). Lifestyle factors associated with lower rates of bone loss (after adjustment for BMI) included alcohol consumption at the femoral neck among women (p = 0.007) and physical activity at the lumbar spine among men (p = 0.05). Serum parathyroid hormone, 25-hydroxyvitamin D and biochemical markers of bone turnover did not predict bone loss after adjustment for adiposity.
Aged↗
Changes in bone mass and bone turnover following distal forearm fracture.
Bone loss occurs close to a fracture and is associated with increased bone turnover. Fracture healing itself results in increased markers of bone turnover. But the exact patterns of these changes after different fractures are unclear. We aimed to investigate the changes in bone density and biochemical markers following distal forearm fracture. Twenty women (mean age 63 years) were recruited following fracture of the distal radius and ulna. Bone mineral density (BMD) of the hand and forearm were measured by dual-energy X-ray absorptiometry (DXA) and quantitative ultrasound (QUS) of the fingers was measured at 0, 6, 12, 26 and 52 weeks after fracture. Serum and urine samples were collected at 0, 3 and 7 days and at 2, 4, 6, 12, 26 and 52 weeks after fracture to measure markers of bone turnover. For bone formation we measured: bone alkaline phosphatase (iBAP), osteocalcin (Oc), procollagen type I N-terminal propeptide (PINP); and for bone resorption: tartrate-resistant acid phosphatase (TRAcP), free deoxypyridinoline (iFDpd), N-telopeptides of type I collagen (NTx). We used the nonfractured limb to calculate values for baseline BMD and amplitude-dependent speed of sound (AD-SoS). There was a decrease in BMD at the hand and in AD-SoS of the fingers after forearm fracture (p<0.001). This bone loss was maximal for BMD by 6 weeks at 9% (p<0. 001) and remained decreased at 52 weeks. AD-SoS decreased at 12 weeks by 3% (p<0.01) and recovered completely by 52 weeks. Bone formation markers increased between 2 and 4 weeks by 13-52% (p<0. 001), and were still elevated at 52 weeks. Bone resorption markers increased between 2 and 6 weeks by 18-35% and returned to baseline at 52 weeks (TRAcP remained elevated). We conclude that BMD decreased distal and immediately proximal to the fracture line when measured with DXA and QUS. Bone loss after distal forearm fracture did not recover by 52 weeks and most bone turnover markers did not return to baseline.
Acid Phosphatase↗
Changes in bone mass and bone turnover following ankle fracture.
Bone loss and increased bone turnover are recognized local changes after a fracture, but the exact patterns of these changes after different fractures are unclear. We aimed to investigate the changes in bone density and biochemical markers following ankle fracture. Fourteen subjects (7 postmenopausal women and 7 men, mean age 63 years) were recruited following fracture of the distal tibia and fibula. Bone mineral density (BMD) of the ankle and proximal femur were measured by dual-energy X-ray absorptiometry (DXA) and quantitative ultrasound (QUS) of the calcaneus at 0, 6, 12, 26 and 52 weeks after fracture. Serum and urine samples were collected at 0, 3 and 7 days and at 2, 4, 6, 12, 26 and 52 weeks after fracture to measure markers of bone turnover. For bone formation we measured: bone alkaline phosphatase (iBAP), osteocalcin (Oc), procollagen type I N-terminal propeptide (PINP); and for bone resorption: tartrate-resistant acid phosphatase (TRAcP), deoxypyridinoline (iFDpd), N-telopeptides of type I collagen (NTx). We used the nonfractured limb to calculate values for baseline BMD and QUS. There was a significant decrease in BMD at the ultradistal ankle (p<0.001), the trochanteric region of the hip (p<0.01) and QUS of the heel after ankle fracture. This bone loss was maximal for ultradistal ankle BMD by 6 weeks at 13% (p<0.001) and for the trochanter by 26 weeks at 3% (p<0.01). The ankle BMD returned to baseline at 52 weeks but the trochanter BMD did not. Velocity of sound (VOS) decreased at 6 weeks by 2% (p<0.01) and broadband ultrasound attenuation (BUA) by 15% (p<0.01). VOS recovered completely by 52 weeks, but BUA did not return to baseline. Bone formation markers increased significantly between 1 and 4 weeks by 11-78% (p<0.01), and iBAP returned to baseline at 52 weeks but PINP and Oc remained elevated. Bone resorption markers did not increase and NTx was decreased at 52 weeks. We conclude that BMD decreased distal and immediately proximal to the fracture line when measured with DXA and QUS. Ankle BMD and heel VOS recovered at 52 weeks (trochanteric BMD and heel BUA did not) and the bone turnover markers returned toward baseline.
Absorptiometry, Photon↗
Diagnosis and management of osteoporosis in postmenopausal women: clinical guidelines. International Committee for Osteoporosis Clinical Guidelines.
The authors, all physicians involved in clinical research on bone and practicing clinicians, propose practical guidelines for identifying persons with osteoporosis or those at high risk of developing the disease and for managing patients who may benefit from therapy. These guidelines are based on an analysis of peer-reviewed articles published before November 1998. A flowchart of women who might benefit from treatment is provided, including clinical presentation (recent fracture of the spine, hip, or other bone or no fracture; risk factors for osteoporosis); relevant investigations (bone mineral density measurement and laboratory tests required for the differential diagnosis); and therapeutic management (general measures such as calcium and vitamin D supplementation and specific pharmacologic interventions such as estrogen, bisphosphonates, intranasal calcitonin, raloxifene, fluoride salts, and other compounds that have been assessed in randomized clinical trials). The strongest evidence for antifracture efficacy (reduction of vertebral and nonvertebral fracture risk) was observed with alendronate.
Adult↗
Measurement of bone mineral density by dual-energy X-ray absorptiometry around an uncemented knee prosthesis.
Dual-energy x-ray absorptiometry allows the measurement of bone mineral density (BMD) around an uncemented hip prosthesis, but has not so far been widely used to measure BMD around a knee prosthesis. We studied 16 patients undergoing total knee replacement using a Miller-Galante uncemented prosthesis for either osteoarthritis or rheumatoid arthritis of the knee. The precision of the measurement was improved by using a leg brace. The pattern of bone loss differed in the lateral projection by region (P = .001). There was significant loss of bone from the distal femur but not from the patella or proximal tibia over the 6-month period after insertion of a knee prosthesis.
Absorptiometry, Photon↗
Biochemical markers of bone turnover in Paget's disease of bone.
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Alkaline Phosphatase↗
Measurement of urinary collagen cross-links indicate response to therapy in patients with breast cancer and bone metastases.
Objective assessment of response in bone metastases from breast cancer using radiological techniques takes up to 6 months of treatment to be certain of a response, and sclerotic metastases are not evaluable. Standard serum and urinary tumour markers may not always be utilized to predict response, as they may not be elevated, and therefore may not change on treatment. The development of the urinary pyridinoline cross-link assays which measure mature bone breakdown products have been shown to be highly sensitive and specific as a measure of bone change in osteoporosis. We have measured pyridinoline (Pyr) and deoxypyridinoline (Dpyr) cross-links sequentially in 36 breast cancer patients with bone metastases, to determine if the measurement of these analytes predicts response at an earlier stage than radiological assessment. Response was assessed by UICC criteria. Seventeen women responded to hormonal therapy, whilst 19 developed progressive disease. Both Pyr and Dpyr increased sequentially in women with progressive disease with changes becoming apparent by 8 weeks (P<0.03). In responding women, cross-link levels did not change significantly. Pyr and Dpyr were more sensitive and specific than the standard serum tumour marker CA 15-3. Urinary cross-link measurements provide a novel objective method of assessing response to treatment in women with bone metastases. Initial elevated urinary cross-link markers identify patients who tend not to respond to changes in hormonal therapy.
Adult↗