The biological features of tumour type, histological grade, vascular invasion, mitotic index, DNA index, and oestrogen receptor (ER) and progesterone receptor (PgR) status have been investigated as prognostic factors in primary operable breast cancer. We have studied these 7 factors in locally advanced primary breast cancer (LAPC): these patients have occult metastases at presentation.Of 60 consecutive patients presenting with locally advanced disease, 36 were treated initially with Tamoxifen and 24 by radiotherapy. Treatment failure was followed by cross-over to the other therapy. All patients were assessed for response in the primary tumour; external review of response was obtained. Survival was compared using the generalised Wilcoxon test.Response to therapy correlated significantly with histological grade (p = 0.02), ER (p = 0.02), PgR status (p = 0.02), mitotic index (p = 0.01), and tumour ploidy (p = 0.04). Survival from initial therapy correlated significantly with ER (p = 0.01) and PgR status (p = 0.04).Histological grade, mitotic index, tumour ploidy, and ER and PgR status of the primary tumour predict response and prognosis in patients with locally advanced (stage III) breast cancer.

Peripheral densitometry is increasingly being used in the management of osteoporosis, but the optimal diagnostic thresholds have not been defined. The aim of this study was to determine the optimal T-score for peripheral dual-energy X-ray absorptiometry (pDXA) of the heel using a GE Lunar PIXI and quantitative ultrasound (QUS) of the heel using a GE Lunar Achilles Plus when compared with dual-energy X-ray absorptiometry (DXA) of central sites (spine, femoral neck, or total hip). Ninety-nine women (mean age 69 +/- 8, range 33-86 yr) referred from the metabolic bone clinic were studied. The optimal T-score for pDXA from ROC analysis was -1.7 and for QUS was -2.5. The pDXA T-score that defined the same prevalence of osteoporosis at any central site was also -1.7 and for QUS was -2.4. These results are similar to the manufacturer's recommendations. There is no significant difference in performance between the PIXI and QUS.

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. (C) 2004 Elsevier Inc. All rights reserved.

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.

: The aim of this project was to compare three phantoms used for cross-calibration of dual-energy X-ray absorptiometers with an in vivo cross-calibration. The phantoms used were the Bona Fide Phantom (BFP), the European Spine Phantom (ESP) and the GE Lunar Aluminum Spine Phantom (ASP). The cross calibration was for L2–L4 lumbar spine bone mineral density (BMD) on a GE Lunar DPX-L and Hologic QDR 2000. The in vivo cross-calibration was obtained using 72 subjects (61 female, 11 male; mean age 49 years, range 14–84 years). The phantoms were measured 10 times without repositioning on both instruments. A further, long-term cross-calibration was obtained with the BFP over a 9 month period. The true linear relationship between the two instruments was calculated used a standardized principal components method. The mean residuals were calculated between each phantom cross-calibration line and the in vivo data to obtain a measure of the goodness of fit between the phantom cross-calibration and the in vivo data. There was no significant difference between the in vitro and in vivo cross-calibrations. The long-term BFP cross-calibration gave an in vitro cross-calibration that is closest to the in vivo cross-calibration in this group of subjects. When calculating Hologic QDR BMD from results on the GE Lunar DPX-L, the ASP underestimates Hologic QDR 2000 BMD by 4% at high BMD and overestimates by 4% at low BMD. The ESP cross-calibration overestimates Hologic QDR2000 BMD by 1% at high BMD and 4% at low BMD. The BFP performs best, overestimating Hologic QDR2000 BMD by between 1.2% and 1.8%, whilst the difference between the long-term BFP cross-calibration and the in vivo data is less than 1% over the range of BMD covered.

Bone scintigraphy has long been used to assess Paget's disease and investigate the response to therapy. Objective visual assessment is, however, difficult. The aim of this study was to derive, from a bone scintigram, an index which objectively measured the extent and severity of Paget's disease in the entire skeleton. This whole body index would provide a single numerical value which could be used to monitor the response to therapy in both monostotic and polyostotic disease. Comparison with other methods of assessing the condition, such as biochemical markers and pain scores, would also be possible. The whole body index was developed and used to retrospectively analyse 80 bone scintigrams on 40 patients. The majority of patients (36) received treatment with a bisphosphonate between the two scintigrams. Whole body index was compared with serum alkaline phosphatase measured at the same time; a significant correlation was found (before treatment P = 0.001, after treatment P<0.001). The change in whole body index and alkaline phosphatase following treatment with various bisphosphonates was also investigated and a significant correlation found (P<0.001). Whilst performing the analysis it was also noted that the increase in uptake of the radiopharmaceutical was significantly greater in the cortical long bones than in the trabecular axial skeleton. This study suggests that a whole body index may be a suitable tool for assessing the response to treatment in Paget's disease.

Quantitative ultrasound (QUS) has been proposed as a tool which can measure both the quantitative and qualitative aspects of bone tissue and can predict the future risk of osteoporotic fractures. However, the usefulness of QUS in long-term monitoring has yet to be defined. We studied a group of early postmenopausal women over a 4-year period. Thirty subjects were allocated to hormone replacement therapy and 30 selected as controls matched for age, years past the menopause (YPM) and bone mineral density (BMD) at the anteroposterior spine (AP spine). The mean age of the subjects was 52.4 years (SD 3.9 years), mean YPM 4.0 years (SD 3.2) and all subjects had a BMD T-score above −2.5 SD (number of standard units related to the young normal mean population). BMD was measured at baseline and annually by dual-energy X-ray absorptiometry (DXA) at the AP spine and total hip, and QUS carried out at the calcaneus, measuring broadband ultrasound attenuation (BUA), speed of sound (SOS) and Stiffness. Mean percentage changes from baseline were assessed at 2 and 4 years. The overall treatment effect (defined as the difference in percentage change between the two groups) was: AP spine BMD, 11.4%; total hip BMD, 7.4%; BUA, 6.4%; SOS, 1.1%; and Stiffness, 10.4% (p<0.01). To compare the long-term precision of the two techniques we calculated the Standardized Precision, which for QUS was approximately 2–3 times that of DXA, for a given rate of change. The ability of each site to monitor response to treatment was assessed by calculating the Treatment Response Index (Treatment Effect/Standardized Precision), which was: AP spine BMD, 10.4; total hip BMD, 3.9; BUA, 3.1; SOS, 0.3; and Stiffness, 4.2. This was then normalized for AP spine BMD (to compare the role of QUS against the current standard, AP Spine BMD), which was: total hip BMD, 0.38; BUA, 0.30; Stiffness, 0.40 (p<0.01); and SOS, 0.03 (NS). In summary, QUS parameters in the early menopause showed a similar rate of decline as AP spine BMD and total hip BMD measured by DXA. Hormone replacement therapy results in bone gain at the AP spine and total hip, and prevents loss in BUA and SOS measured by QUS at the calcaneus. QUS has a potential role in long-term monitoring, although presently the time period to follow individual subjects remains 2–3 times that for DXA, for a given rate of change. Anteroposterior spine remains the current optimal DXA monitoring site due to its greater rate of change and better long-term precision.

: In this study we report first the concordance and variation in diagnostic osteoporosis classification using multiple skeletal site measurements compared with the lumbar spine only; and secondly, at the lumbar spine, the variation and diagnostic osteoporosis reclassification using the lowest individual vertebra T -score compared with the L1–L4 mean T -score. One hundred and fifty early postmenopausal women were evaluated as part of the recruitment for a multicenter osteoporosis prevention study. Bone mineral density (BMD) was restricted such that no more than 10% of the subjects had a lumbar spine BMD below 0.8 g/cm 2 . Forty-seven per cent of the subjects were classified as having low bone mass ( T -score ≤−1.0) at the lumbar spine, 63% at the mid-forearm, 39% at the distal forearm and 50% at the hip ( p <0.05). The greatest proportion of subjects were categorized as osteoporotic at the lumbar spine, followed by the forearm and then the hip. Correlation between sites ranged from 0.57 to 0.60 ( p <0.01). Eighty-one percent of the subjects had a significant difference between their highest and lowest individual lumbar vertebra T -score (defined as a difference outside the 90% confidence interval coefficient of variation T -score value). Using the lowest individual lumbar T -score, recategorized 33% of the subjects classified as osteopenic (based on the mean L1–L4 T -score) as osteoporotic, and 23% of those classified as normal as osteopenic ( p <0.05). Of all four vertebrae, L2 had the highest T -score in 37.7% of the subjects (mean −0.3) and L4 the lowest in 61% (mean −1.5) (mean difference 1.2 units, 95% CI 0.7 to 1.7). The classification of osteoporosis varies according to skeletal site, with pronounced differences in the early menopausal population. T -scores are useful for characterizing subjects with the highest risk of osteoporosis but BMD and fracture risk must be recognized in a continuum. Individual T -scores of the lumbar vertebrae show wide variation in the absence of degenerative spinal disease or vertebral collapse and the use of the lowest, significantly different, individual lumbar vertebra T -score reclassified over half of the subjects in this study. This poses a great therapeutic dilemma in clinical practice, particularly if these fractures are at higher risk of future collapse.

The aim of this cross-sectional study was to use a novel method of data analysis to demonstrate that patients with osteoporosis have significantly lower ultrasound results in the heel after correcting for the effect of bone mineral density (BMD) measured in the spine or hip. Three groups of patients were studied: healthy early postmenopausal women, within 3 years of the menopause (n=104, 50%), healthy late postmenopausal women, more than 10 years from the menopause (n=75, 36%), and a group of women with osteoporosis as defined by WHO criteria (n=30, 14%). Broadband ultrasound attenuation (BUA), speed of sound (SOS) and Stiffness were measured using a Lunar Achilles heel machine, and BMD of the lumbar spine and left hip was measured using dual-energy X-ray absorptiometry (DXA). SOS, BUA and Stiffness were regressed against lumbar spine BMD and femoral BMD for all three groups combined. The correlation coefficients were in the range 0.52–0.58, in agreement with previously published work. Using a calculated ratio R, analysis of variance demonstrated that the ratio was significantly higher in the osteoporotic group compared with the other two groups. This implied that heel ultrasound values are proportionately lower in the osteoporotic group compared with the other two groups for an equivalent value of lumbar spine and femoral neck BMD. We conclude that postmenopausal bone loss is not associated with different ultasound values once lumbar spine or femoral neck BMD is taken into account. Ultrasound does not give additional information about patterns of bone loss in postmenopausal patients but is important in those patients with osteoporosis and fractures.

A cross-sectional study of bone density involving 30 patients who had undergone orchidectomy and para-aortic radiotherapy for Stage I seminoma of the testis, has been performed. Bone density measurements were made of the whole body, lumbar spine and hips, including all irradiated areas. Comparison was made with previously obtained standard sex and age matched control data. The 30 patients treated for seminoma had a significantly increased mean bone density compared with age matched normal values. No significant differences were demonstrated between the mean bone densities of the irradiated and non-irradiated hips. There was no significant relationship between bone density measurement and time since orchidectomy or radiotherapy. These results suggest that nodal irradiation for seminoma has little long term effect on bone density.