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Biomedical subjects

D Hosking

Publications and source records attributed to D Hosking.

At least 19 recordsLinked to original sources
PubMed2006

The prevalence of vitamin D inadequacy amongst women with osteoporosis: an international epidemiological investigation.

INTRODUCTION: Vitamin D is essential for calcium metabolism as well as for fracture prevention, and a recent review suggested that the optimal serum 25(OH)D lies in the region of 50-80 nmol L-1 (20-32 ng mL-1). A high prevalence of inadequacy has been reported in many studies but the prevalence of inadequacy amongst women with osteoporosis in different regions of the world has not been well characterized. SETTING AND SUBJECTS: A multinational study of 18 countries at various latitudes (range 64N-38S) was conducted in 2004 and 2005 to determine the average levels of serum 25(OH)D and the prevalence of vitamin D inadequacy. A total of 2606 postmenopausal women with osteoporosis (low bone mineral density, history of fragility fracture) seeking routine medical care were enrolled and serum 25(OH)D levels were measured at a single laboratory visit. RESULTS: Mean serum 25(OH)D level was 26.8 ng mL-1 (SE 0.3) and ranged from 7 to 243 ng mL-1. Regional mean values were highest in Latin America (29.6 ng mL-1, SE 0.6) and lowest in the Middle East (20.4 ng mL-1, SE 0.5). Overall, 64% of women had serum levels<30 ng mL-1. Serum parathyroid hormone reached a nadir at serum 25(OH)D levels>35 ng mL-1. In nonequatorial countries, women recruited during the winter months had somewhat lower serum 25(OH)D levels than those recruited during the summer months in some, but not all, countries. CONCLUSIONS: Low levels of serum 25(OH)D are common amongst women with osteoporosis. The results underscore the value of assuring vitamin D adequacy in these women.

Adult↗
PubMed2004

Recovery of pregnancy mediated bone loss during lactation.

It is uncertain whether bone is routinely mobilised during pregnancy to provide calcium for the fetus and whether this is of a magnitude to cause osteoporosis. We have made sequential measurements of lumbar spine and hip bone mineral density (BMD) in 60 normal women before conception and then during the subsequent pregnancy out to one year after delivery. During pregnancy there was a significant fall in the BMD at the spine (1.53%), total hip (1.15%), and trochanter (3.90%) but not at the femoral neck. After delivery the women who breast-fed (n=34) showed a significant fall in BMD at all measurement sites (P<0.001) with the greatest change at the spine (4.7 +/- 3.1%) with 38% of women showing a change >5%. The women who bottle fed (n=10) increased or maintained BMD at all sites with the mixed feeders (n=16) showing an intermediate response. There was no consistent relationship between the change during pregnancy and lactation but 47% of the breast-feeders lost >5% at either the lumbar spine or trochanter. There was a good correlation between the change in BMD at these two sites (r=0.48, P<0.001). At 1 year after delivery all but 7 women had returned to within 5% of the preconceptual value at the spine and trochanter but the recovery at the total hip was less complete. Several women became transiently osteoporotic (T score below -2.5) at either spine or hip during reproduction of whom three started pregnancy with a normal BMD.

Adult↗
PubMed2003

Longitudinal changes in bone mineral density during normal pregnancy.

Pregnancy is a common physiological event that could affect peak bone mass and the risk of developing osteoporosis later in life. There have been few longitudinal studies over a complete reproductive cycle of any size to show whether bone mineral density (BMD) changes. We have measured BMD by dual-energy X-ray absorptiometry in 46 normal women before conception and then again immediately after delivery and compared them with 30 control women who failed to conceive. Fifteen women were osteopenic in preconceptual BMD, but there was no difference between those who did or did not become pregnant. During pregnancy there was a small and statistically nonsignificant decline in BMD at all sites. The decrease at the trochanteric region was 4.2%, while losses at other sites were about 1%. The decline at the trochanter exceeded the least significant change between two measurements (5.04%) in 17 women (40.5%) with significant changes within individuals being much less common at the other measurement sites. The nonpregnant controls showed small increases in BMD of 0.3%-1.9% but no woman lost more than the least significant change. At the trochanter there was a significant difference (P = 0.013) between those who did and did not become pregnant. There was a good correlation between changes in BMD at all sites and no significant difference in the slope of these correlations between the pregnant and control groups. Correlations with lumbar spine were total hip, r = 0.46, P = 0.0001; femoral neck, r = 0.49, P = 0.0005; and trochanter, r = 0.66, P < 0.0001.

Absorptiometry, Photon↗
PubMed2000

Relation between body composition and biochemical markers of bone turnover among early postmenopausal women.

We studied the associations between body composition and biochemical markers of bone formation and resorption among 1600 postmenopausal women, ages 45-59. Multiple regression analyses were performed to examine the independent associations of fat mass, muscle strength (quadriceps strength), height, and whole body bone mineral content (BMC) with biochemical markers of bone formation (serum osteocalcin) and resorption (urinary type I collagen crosslinked N-telopeptides [NTX]). Per interquartile range (IQR) (the difference between 75th and 25th percentiles) increase in fat mass and whole body BMC, the mean levels of osteocalcin decreased by 3% and 13%, respectively; NTX decreased by 5 and 21%. Fat mass and whole-body BMC were also significantly associated with decreases in the average of osteocalcin and NTX Z-scores. By contrast, the mean levels of serum osteocalcin increased by 2 and 11%, respectively, per IQR increase in muscle strength and height; NTX increased by 4 (not significant) and 14%, respectively. Both muscle strength and height were significantly associated with increases in the average Z-scores. These exploratory analyses suggest that fat mass and whole-body BMC were associated with decreased bone turnover, while muscle strength and height were associated with increased bone turnover.

Adipose Tissue↗
PubMed1999

Monitoring of alendronate treatment and prediction of effect on bone mass by biochemical markers in the early postmenopausal intervention cohort study.

To establish whether biochemical markers could be used to monitor alendronate (ALN) treatment and predict long-term response in bone mass, we used results from an ongoing, randomized trial of ALN treatment for prevention of postmenopausal osteoporosis (n = 1202). In women treated with ALN (5 mg), change from baseline at month 6 in urine N-telopeptide cross-links of type I collagen (NTX) and osteocalcin (OC) correlated with change from baseline at month 24 in spine, hip, and total body bone mineral density (BMD) [r = -0.28 to -0.31 (NTX) and r = -0.16 to -0.25 (OC), P<0.001]. This corresponded to a 4- to 5-fold greater increase at month 24 in BMD in the tertiles, with the greatest decrease at month 6 in NTX or OC. In women treated with ALN (5 mg) who had a change at month 24 in spine BMD of at least 0%, 86% (NTX) and 79% (OC) had a decrease at month 6 of at least 40% (NTX) or 20% (OC) (sensitivity). The corresponding specificities were 48% (NTX) and 53% (OC). In conclusion, change at month 6 in NTX and OC, in groups of women treated with ALN, indicated the numeric long-term response in BMD within these groups. In individual women, a decrease at month 6, in NTX or OC below the cut-point, validly identified women who responded, on ALN treatment, with a stabilization or an increase in bone mass. However, lack of decrease below the cut-point in NTX or OC could not be used to identify women with a bone loss during ALN treatment.

Alendronate↗
PubMed1999

Low body mass index is an important risk factor for low bone mass and increased bone loss in early postmenopausal women. Early Postmenopausal Intervention Cohort (EPIC) study group.

Thinness (low percentage of body fat, low body mass index [BMI], or low body weight) was evaluated as a risk factor for low bone mineral density (BMD) or increased bone loss in a randomized trial of alendronate for prevention of osteoporosis in recently postmenopausal women with normal bone mass (n = 1609). The 2-year data from the placebo group were used (n = 417). Percentage of body fat, BMI, and body weight were correlated with baseline BMD (r = -0. 13 to -0.43, p < 0.01) and 2-year bone loss (r = -0.14 to -0.19, p < 0.01). Women in the lowest tertiles of percentage of body fat or BMI had up to 12% lower BMD at baseline and a more than 2-fold higher 2-year bone loss as compared with women in the highest tertiles (p </= 0.004). Women with a lower percentage of body fat or BMI had higher baseline levels of urine N-telopeptide cross-links (r = -0.24 to -0.31, p < 0.0001) and serum osteocalcin (r = -0.12 to -0.15, p < 0.01). To determine if the magnitude of treatment effect of alendronate was dependent on these risk factors, the group treated with 5 mg of alendronate was included (n = 403). There were no associations between fat mass parameters and response to alendronate treatment, which indicated that risk of low bone mass and increased bone loss caused by thinness could be compensated by alendronate treatment. In conclusion, thinness is an important risk factor for low bone mass and increased bone loss in postmenopausal women. Because the response to alendronate treatment is independent of fat mass parameters, prevention of postmenopausal osteoporosis can be equally achieved in thinner and heavier women.

Alendronate↗
PubMed1999

Out-patient hysteroscopy in asymptomatic postmenopausal women.

OBJECTIVE: To determine the prevalence of uterine and endometrial abnormalities in normal postmenopausal women and assess the accuracy of subjective hysteroscopic appearances and endometrial histology following 12 weeks of hormonal treatment. DESIGN: A multicentered randomized double-blind placebo-controlled trial in which the volunteers received conjugated equine estrogen 0.625 mg, selective estrogen receptor modulator (in one of two doses) or placebo. SETTING: Out-patient endoscopy unit in a large teaching hospital. METHODS: Out-patient hysteroscopy and endometrial biopsy. RESULTS: Forty-eight women had a hysteroscopy and endometrial biopsy: eight (16.6%; 95% confidence interval, CI 6-27%) women had intrauterine polyps and 38 (79.2%) women had normal hysteroscopies. Thirty-five women had a repeat endometrial assessment with hysteroscopy and, for the detection of proliferative endometrium (prevalence 22.8%), a sensitivity of 87.5%, a specificity of 74%, a negative predictive value of 95% and a positive predictive value of 50% were observed. There was a good proportion of agreement, 0.77 (95% CI 0.63-0.91), but a kappa score of 0.486 revealed only a moderate level of agreement. The likelihood ratios for proliferative endometrium were: LHR+ = 3.38 (fair), and LHR- = 0.17 (moderate). CONCLUSIONS: Hysteroscopic assessment of the uterine cavity is efficient in the detection of pathological intrauterine lesions, but is only moderately successful in determining physiological changes in the endometrium. This study defines a standard of observational statistics for out-patient hysteroscopy in relation to normal endometrial histology in postmenopausal women who may have been ingesting exogenous estrogens.

Ambulatory Care↗
PubMed1998

Prevention of bone loss with alendronate in postmenopausal women under 60 years of age. Early Postmenopausal Intervention Cohort Study Group.

BACKGROUND: Estrogen-replacement therapy prevents osteoporosis in postmenopausal women by inhibiting bone resorption, but the balance between its long-term risks and benefits remains unclear. Whether other antiresorptive therapies can prevent osteoporosis in these women is also not clear. METHODS: We studied the effect of 2.5 mg or 5 mg of alendronate per day or placebo on bone mineral density in 1174 postmenopausal women under 60 years of age. An additional 435 women who were prepared to receive a combination of estrogen and progestin were randomly assigned to one of the above treatments or open-label estrogen-progestin. The main outcome measure was the change in bone mineral density of the lumbar spine, hip, distal forearm, and total body measured annually for two years by dual-energy x-ray absorptiometry. RESULTS: The women who received placebo lost bone mineral density at all measured sites, whereas the women treated with 5 mg of alendronate daily had a mean (+/-SE) increase in bone mineral density of 3.5+/-0.2 percent at the lumbar spine, 1.9+/-0.1 percent at the hip, and 0.7+/-0.1 percent for the total body (all P<0.001). Women treated with 2.5 mg of alendronate daily had smaller increases in bone mineral density. Alendronate did not increase bone mineral density of the forearm, but it slowed the loss. The responses to estrogen-progestin were 1 to 2 percentage points greater than those to the 5-mg dose of alendronate. Alendronate was well tolerated, with a safety profile similar to that of placebo or estrogen-progestin. CONCLUSIONS: Alendronate prevents bone loss in postmenopausal women under 60 years of age to nearly the same extent as estrogen-progestin.

Alendronate↗
PubMed1998

Diagnosis and treatment of prostatitis in Canada.

OBJECTIVES: There is a general consensus among physicians that the present management of chronic prostatitis is dismal. We undertook a survey of Canadian primary care physicians (PCPs) and urologists to determine the degree and source of frustration and to analyze present practice patterns in this disease. METHODS: Five thousand PCPs and all 545 Canadian urologists were asked to complete a comprehensive computer-assisted telephone survey that explored practice characteristics, attitudes, and diagnostic and treatment strategies in the management of prostatitis. Randomization of attribute banks, adherence to questionnaire routing, validation by on-site monitoring, and possible bias were addressed. RESULTS: Completed interviews were obtained from 10% of PCPs and 28% of urologists. PCPs see on average 3.5 (median 2) patients with prostatitis per month and urologists see on average 21.8 (median 11) patients with prostatitis per month. All physicians experience significantly more frustration in treating prostatitis than they do in treating patients with benign prostatic hyperplasia (BPH) and prostate cancer, and they perceive that prostatitis affects patients' quality of life significantly more than BPH and almost as much as prostate cancer. The degree of frustration and unhappiness in dealing with prostatitis is driven by a lack of confidence and comfort in their ability to accurately diagnose and subsequently rationalize treatment. Most PCPs and urologists continue to employ steps in addition to history and physical examination to establish a diagnosis but only a few PCPs and a third of urologists use specific lower urinary tract cultures. Physicians tend to use trimethoprim or trimethoprim-sulfamethoxazole (TMP-SMX) or a fluoroquinolone as their usual first line therapy for chronic prostatitis. The most commonly used therapeutic strategy (40%) for chronic prostatitis was TMP-SMX as first line therapy and a fluoroquinolone as second line therapy. CONCLUSIONS: There is widespread frustration, discomfort, and lack of confidence in both PCPs' and urologists' perceived ability to manage prostatitis. Physicians have expressed a desire for a better understanding of this disease, simpler and clearer diagnostic guidelines, and more rational treatment strategies.

Canada↗
PubMed1998

Pagetic osteoclasts formed in vitro: absence of paracrystalline inclusions.

In Paget's disease of bone, osteoclasts are increased in number and size and contain intracellular paramyxoviral-like inclusions which cross-react with antibody against measles, respiratory syncytial, and canine distemper viral nucleocapsid antigens. Moreover, measles virus nucleocapsid transcripts are present in pagetic osteoclasts and their mononuclear precursors formed in vitro. The present study was undertaken to morphologically assess pagetic osteoclasts formed in culture; special attention has been directed towards the ultrastructural identification of nuclear and cytoplasmic inclusions. Pagetic osteoclasts were produced in long-term cultures of non-adherent bone marrow mononuclear cells derived from involved bone of patients with Paget's disease. These cultured osteoclasts had many of the ultrastructural features of pagetic osteoclasts in vivo. Of interest, no viral-like inclusions were observed in either the multinucleated osteoclasts or mononuclear cell precursors in these cultures. These data suggest that other factors in the bone microenvironment are required for viral nucleocapsid formation in pagetic osteoclasts.

Bone Marrow Cells↗
PubMed1997

Pituitary dysfunction in recently post-menopausal women. Nottingham EPIC Study Group.

OBJECTIVE: Some recently post-menopausal women have lower than expected FSH concentrations, raising the possibility of subclinical hypothalamo-pituitary impairment. We have therefore performed pituitary stimulation tests in a group of recently post-menopausal women recruited to a bone loss prevention study. DESIGN: Prospective study of health volunteers. SETTING: Outpatient, teaching hospital in Nottingham UK. SUBJECTS: Forty-seven women selected from a cohort of 428 healthy volunteers to an osteoporosis prevention study all within 10 years of the menopause. MAIN OUTCOME MEASURES: Response of the pituitary to formal stimulation tests and its relationship to bone mineral density. RESULTS: A significantly attenuated response to pituitary stimulation was found in a group of otherwise healthy women with an FSH considered to be inappropriately low for the level of circulating oestradiol. The impaired responses were significant not only for FSH as expected but also to LH and prolactin at 1 hour after injection of GnRH and TRH (area under the curve, FSH P = 0.01, LH P = 0.001, prolactin P < 0.0001). TSH secretion was not significantly impaired. Baseline cortisol, growth hormone and thyroxine (T4) were normal in both control and test subjects. The test group was both heavier and taller, with a higher lean body mass, a higher body mass index and a greater total body fat than the controls. Bone mineral density showed no significant differences between the groups. Test subjects also had a higher free oestradiol index (P < 0.001) which correlated strongly (r = 0.534, P = 0.00026) with baseline FSH levels and possibly reflects a greater tissue exposure to biologically active hormone. Oestrone concentrations were, however, no different between the groups. CONCLUSIONS: Serum FSH concentrations are not invariably elevated in recently post-menopausal women and use of FSH as a determinant for postmenopausal status in clinical trials should be used with caution. Notwithstanding their higher free oestradiol index, women found to have an abnormally low basal FSH had evidence of poor prolactin, FSH and LH but not TSH responses to pituitary stimulation. This may represent either a degree of subclinical pituitary failure of a variant of normal. The low levels of gonadotrophin activity did not affect bone mineral density.

Bone Density↗
PubMed1996

Oral alendronate induces progressive increases in bone mass of the spine, hip, and total body over 3 years in postmenopausal women with osteoporosis.

To determine the effects of long-term daily oral alendronate sodium (ALN) on bone mass in postmenopausal women with osteoporosis, 19 centers enrolled 516 postmenopausal women aged 45-80 years with spine bone mineral density (BMD) at least 2.5 SD below the mean for young premenopausal women in a 3-year, double-blind, placebo-controlled study. Subjects were randomly allocated to one of four treatment groups: placebo; alendronate, 5 or 10 mg/day for 3 years; or alendronate, 20 mg/day for 2 years followed by 5 mg/day for the 3rd year. All patients received 500 mg/day of supplemental calcium to ensure adequate calcium intake. BMD was measured by dual-energy X-ray absorptiometry at several skeletal sites. Nonsignificant mean decreases in BMD of the spine, femoral neck, and trochanter of 0.6, 0.7, and 0.4%, respectively, occurred in the placebo group at 3 years. Relative to placebo-treated patients, spine BMD increased by 5.4%, 7.4%, and 8.4% in the 5, 10, and 20/5 mg ALN groups, respectively. Increases at the femoral neck were 3.5%, 5.5%, and 4.3%, and those at the trochanter were 5.1%, 7.2%, and 7.2%, respectively. Thus, efficacy of 10 and 20/5 mg ALN was similar, whereas the 5 mg dose was less effective. BMD continued to increase over the entire 3-year study duration in the ALN-treated groups and, compared with the other dosage groups, 10 mg ALN produced the largest gains in BMD during the 3rd year. Changes in biochemical markers of bone turnover and mineral homeostasis confirmed the effect of ALN to decrease bone turnover to a new steady-state level. The safety and tolerability of ALN were comparable with those of placebo. In summary, 10 mg daily oral ALN given for 3 years significantly and progressively increases bone mass and is a generally well-tolerated treatment for osteoporosis in postmenopausal women.

Administration, Oral↗
PubMed1992

Interleukin 6. A potential autocrine/paracrine factor in Paget's disease of bone.

Pagetic osteoclasts are greatly increased in number and size and have increased numbers of nuclei per cell compared to normal osteoclasts. The mechanisms responsible for enhanced osteoclast formation in Paget's disease are unknown. We have used our recently described model system for pagetic osteoclast formation to evaluate culture media conditioned by these atypical multinucleated cells (MNC) to determine if pagetic osteoclasts produce an autocrine or paracrine factor that enhances osteoclast formation. Conditioned media from long-term bone marrow cultures from patients with Paget's disease stimulated osteoclast-like MNC formation in normal marrow cultures. At least part of this activity could be ascribed to interleukin 6 (IL-6). In contrast, conditioned media from normal marrow cultures contained lower levels of IL-6 and did not stimulate formation of osteoclast-like MNC. 7 of 8 bone marrow plasma samples taken from involved bones and 18 of 27 peripheral blood serum samples from Paget's patients had high levels of IL-6. Normal marrow plasma and peripheral blood serum had no or very low levels of IL-6. These results suggest that IL-6 produced by marrow and/or bone cells in patients with Paget's disease may be an autocrine/paracrine factor for pagetic osteoclasts.

Biological Assay↗
PubMed1991

Inorganic pyrophosphate in metabolic diseases predisposing to calcium pyrophosphate dihydrate crystal deposition.

Inorganic pyrophosphate (PPi) levels were estimated by radiometric assay in urine and in synovial fluid (SF) from asymptomatic, nonarthritic knees of patients with untreated metabolic disease and normal controls. SF PPi was significantly elevated in patients with hyperparathyroidism (mean +/- SEM 19 +/- 3 microM; n = 9), hemochromatosis (23 +/- 5 microM; n = 6), and hypomagnesemia (27 +/- 0.1 microM; n = 2) compared with normal subjects (10 +/- 0.5 microM, n = 50), and was low in patients with hypothyroidism (4.2 +/- 2.3 microM; n = 11) (P less than 0.05 all comparisons). Urinary PPi was elevated only in those with hypophosphatasia. Local elevation of ionic PPi may be relevant to the mechanism of crystal formation in metabolic diseases predisposing to calcium pyrophosphate dihydrate (CPPD) crystal deposition. The finding of low SF PPi levels in patients with hypothyroidism further questions the association between this condition and CPPD.

Adult↗
PubMed1991

The diphosphonate space: a useful quantitative index of disease activity in patients undergoing hydroxy methylene diphosphonate (HMDP) bone imaging for Paget's disease [corrected].

Comparison between the plasma levels of intravenously injected technetium 99m hydroxy methylene [corrected] diphosphonate (99mTc-HMDP) and chromium 51 ethylene diamine tetra-acetic acid (51Cr-EDTA) reflects the uptake of diphosphonate into bone (the diphosphonate space). This can be used as an index of skeletal function in metabolic bone disease. In a series of 49 patients with Paget's disease the diphosphonate space (DPS) correlated well with other indicators of disease activity such as alkaline phosphatase and urinary hydroxyproline levels. The DPS is a good predictor of the volume of skeletal involvement as estimated from bone images. The DPS also provides a sensitive indicator of response to treatment with intravenously administered bisphosphonate. The DPS is simple to perform and is a useful adjunct to routine bone imaging.

Alkaline Phosphatase↗