Search

Premenopausal women receiving chemotherapy or endocrine treatment for early breast cancer are at increased risk for cancer treatment induced bone loss (CTIBL). The aim of the randomized, double-blind ProBONE II trial was to investigate whether a 2-year adjuvant treatment with 4 mg intravenous zoledronic acid (ZOL) every 3 months versus placebo would prevent CTIBL after a five-year period.Thirty-one of the 34 participants in the ZOL arm and thirty-four of the 36 participants in the placebo arm were followed-up to the 5-year visit and completed the study as planned. The changes in Bone Mass Density (BMD) were assessed at baseline and each visit after treatment initiation.After 24 months, BMD at the lumbar spine showed a 2.9% increase in patients treated with ZOL vs. a 7.1% decrease in placebo-treated participants compared to baseline (p 0.001). Over the 60-month study period, we found a decrease of 2.2% vs. 7.3% in the BMD at the lumbar spine in patients receiving ZOL and placebo respectively (p 0.001). Over the 60-month study period, BMD in the placebo arm showed a continuous decrease at all sites (p 0001), whereas patients treated with ZOL reached baseline BMD-values at the femoral neck and total hip.In ProBone II, a 2-year treatment with ZOL 4 mg intravenous every 3 months prevented cancer treatment induced bone loss in premenopausal women with breast cancer and maintained the BMD up to 3 years post-treatment.

This study describes bone mass changes during pregnancy and lactation measured by a special ultrasound method. Pregnant women showed a decrease of bone mass followed by a stable bone mass while breast-feeding afterwards. Later in life, there is a recovery of bone mass loss.The aim of this study was to evaluate bone changes during pregnancy using the radiation-free method of quantitative ultrasonometry (QUS).One hundred twenty-five pregnant women who underwent prenatal care were included in this study. Ultrasound measurement of the calcaneus was performed in each trimester and then 6 weeks, 3 months, and 1 year postpartum. The calcaneal QUS measurements were carried out using the Achilles plus device (GE/Lunar Corporation, Madison, WI). Three ultrasound variables were measured: speed of sound (SOS, m/s), broadband ultrasound attenuation (BUA, dB/MHz), and the "stiffness index" (expressed as the percentage of the mean value in young adults). SOS and BUA raw data result in the t-score and z-score.A complete panel of six measurements was acquired over the time period in 101 patients (80.8%). Forty-two percent of the included patients were primipara, while 58% had given birth to at least one child (47%) previously. There was a statistically significant change of the t-score (tv = 2.14, p = 0.035) and the stiffness index (tv = 2.46, p = 0.016) from the second to the third trimester, followed by a plateau during lactation. Interestingly, the t-score remained stable during lactation, regardless of the duration of lactation (3 months, 3-6 months, and6 months).Young primiparas who had a sedentary adolescence were at the highest risk of bone loss during pregnancy. Bone loss that occurred during pregnancy was typically recovered later on, based on unknown molecular and biochemical mechanisms that must be elucidated with further studies.

Adjuvant treatment for hormone receptor-positive breast cancer in postmenopausal women with aromatase inhibitors is associated with increased bone loss depending on the compliance to treatment.In this bone substudy, bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry at baseline and after 12- and 24-month treatment in 63 patients receiving Anastrozole as adjuvant treatment for hormone receptor-positive early breast cancer. To minimize the effects of confounders, a matched pair analysis (compliant N = 21, non-compliant N = 21) was performed.Anastrozole treatment in compliant patients leads to a decrease in BMD (g/cm(2)) at lumbar spine and total hip from baseline to 12 and 24 months (-2.57 % P = 0.004; -2.02 % P = 0.05; -2.57 % P = 0.001 and -4.18 % P = 0.003, respectively) compared to non-compliant patients (-1.71 % P = 0.050; -2.00 % P = 0.085; -1.65 % P = 0.055 and -3.20 % P = 0.005, respectively).Anastrozole treatment in compliant patients with breast cancer resulted in a larger, increase in bone loss at 12 and 24 months compared to non-compliant patients. Bone loss stabilized in both groups at the spine from 12- to 24-month treatment, whereas maintained at the total hip.

The etiology and underlying mechanisms of transient of osteoporosis of the hip (TOH) during pregnancy are still unclear, since no systematic analyses exist. Our results support the hypothesis that TOH is a multifactorial disease, which is associated with immobility, dental problems, and lack of exercise in childhood. Pregnancy-associated transient osteoporosis of the hip (TOH) is a rare but severe form of osteoporosis, which may affect a subgroup of women in the last trimester of pregnancy or immediately postpartum. Common symptoms include acute pain of the hip(s) due to bone marrow edema or even hip fractures. The exact underlining mechanisms of this disorder are still unknown since no published systematic analyses exist. Out of a total of 52 TOH patients, 33 TOH patients could be matched with 33 healthy controls according to age, region, and gravity. The aim of this retrospective case-control study was to evaluate the risk factors for TOH in a homogenous population of women. The baseline characteristics of the two study groups were similar. Overall, 12.1% of the TOH patients sustained a hip fracture. Expectedly, 90.9% of the TOH patients complained about pain of the hip (p ≤ 0.001). TOH patients suffered more frequently from severe dental problems during childhood (p = 0.023) and performed less often sports before and after puberty (p ≤ 0.001), whereas the frequency of immobilization during pregnancy was threefold higher compared to the control group (p = 0.007). We found a significant increase of the TOH risk in patients with dental problems in childhood (OR 3.7; CI 1.3–10.7) as well as in patients with lack of exercise during childhood (OR 4.2; CI 1.3–12.9). Our results support the hypothesis that pregnancy-associated TOH is a multifactorial disease, to which several individual factors may contribute. Hereby, we found significant associations with immobility, dental problems, and lack of exercise in childhood.

This cross-sectional study updated age changes for ultrasonometry (QUS) of the os calcis in a large sample of healthy German women. The speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness index (SI) of the os calcaneus were measured in 5148 women (mean age 55.2 ± 10.6 yr) using the Achilles ultrasonometer (GE/Lunar). There was an overall decline of 16% for BUA, 4% for SOS, and 32% for SI between late adolescence and old age. In premenopausal women, BUA decreased only slightly (–2%), whereas postmenopausal women showed a significantly increased decline (–12%). In contrast, SOS continuously decreased from the age of 15; there was a decline of 2% from adolescence to menopause. The SI of premenopausal women decreased only by 9%, but the postmenopausal decline of almost 21% was significantly greater. In accordance to our previous report, the age regression for SI in the larger sample differed from the earlier sample, indicating an increased bone loss with aging after the menopause. The SI values in premenopausal German women were comparable to those for British and American women 20–50 yr of age. After age 50, the SI of German women was significantly 3–7% higher in comparison to the British and American reference population.

While their negative impact on bone health is well established, the effects of aromatase inhibition (AI) on Wnt inhibitors and osteoprotegerin (OPG) are unknown. The aim of the study was to investigate the effects of AI on serum levels of sclerostin, DKK-1 and OPG, as well as their associations with PINP and CTX as markers of bone turnover and bone mineral density (BMD) assessed by DXA.We conducted a prospective longitudinal analysis of 70 postmenopausal women with hormone receptor-positive early breast cancer (BC) treated with anastrozole. All measurements were performed at baseline, 12 and 24 months of treatment. We measured the association of the investigated variables with circulating bone turnover markers, as well as with the BMD.After 24 months of AI therapy, sclerostin and OPG concentrations increased from 29.5 pmol/l (SD = 15.1) and 6.8 pmol/l (SD = 2.2) at baseline to 43.2 pmol/l (SD = 20.6) (p0.001) and 7.4 pmol/l (SD = 2.2) (p = 0.028), respectively. DKK-1 levels decreased from 34.3 pmol/l (SD = 13.5) at baseline to 29.7 pmol/l (SD = 12.3) at the 24-month visit (p = 0.005). Sclerostin levels significantly correlated with PTH, OPG and BMD of the lumbar spine, while DKK-1 correlated with the BMD of the femoral neck and of the total hip.The observed increase in sclerostin levels indicates a central role of osteocytes in bone turnover in women with BC.

This study aimed to evaluate the influence of hormone replacement therapy (HRT), the estradiol concentration and body mass index (BMI, kg/m(2)) on the serum leptin concentration in postmenopausal women.352 healthy postmenopausal women (mean age, 60.9 +/- 8.5 years) participated in this comparative study. 71 (30%) women (mean age 55.9 +/- 8.3 years) had taken HRT, while 281 (70%) women (mean age, 59.1 +/- 10.6 years) had not. Baseline characteristics -age, weight, height, BMI (greater than or = 25 or25), follicle stimulating hormone, estradiol, and leptin values-were compared in the two groups. In a second analysis to evaluate the influence of HRT, estradiol concentrations, and BMI on leptin concentrations, these data were analysed in women allocated to one of four groups: (a) postmenopausal women not on HRT with a BMI25 (n = 130); (b) postmenopausal women not on HRT with a BMI greater than or = 25 (n = 151); (c) postmenopausal women on HRT with a BMI25 (n = 48); and (d) postmenopausal women on HRT with a BMI greater than or = 25 (n = 23). Leptin concentrations were subsequently analysed in relation to BMI and age and BMI and estradiol concentrations to determine any independent effect of these variables.The women taking HRT had a significantly lower mean age, weight, BMI and follicle stimulating hormone concentration than those who were not taking HRT. Furthermore, they had a higher mean height and serum estradiol value, but a significantly lower serum leptin concentration. After controlling for BMI, neither the use of HRT nor the estradiol concentration was found to be related to the leptin value (group (a) versus (c) and group (b) versus (d)), but there were significant differences in leptin concentrations between HRT users with BMI greater than or = 25 and BMI25 and between women not taking HRT with BMI greater than or = 25 and BMI25 (groups (a) versus (b) and (c) versus (d)). Furthermore, women with a BMI greater than or = 25 had significantly higher leptin concentrations than women with a BMI25, irrespective of the HRT use.Leptin concentrations are significantly higher in obese postmenopausal women than in their non-obese counterparts. Serum leptin concentrations are not influenced by HRT use or estradiol concentrations. Further studies are needed to elucidate the role of HRT and estrogen on serum leptin concentrations.

Quantitative ultrasonometry (QUS) of the os calcis has been shown to predict hip fracture in late postmenopausal women, and vertebral and forearm fracture in early postmenopausal women. Speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness index (SI) of the os calcis were measured using the Achilles ultrasonometer (Lunar, Madison, WI). Osteoporosis risk factors were assessed by a detailed questionnaire. We examined 1314 normal women from age 48 to 79 yr, with a mean age 60 +/- 7.5 yr. In addition, we examined women of similar age, of whom 80 had suffered a hip fracture and 40 a spine fracture. The short-term precision in vivo expressed as the coefficient of variation was 1.2% for BUA, 0.2% for SOS, and 1.3% for SI. A total of 813 women were measured at both the right and left heel. There was high correlation between the two sides (r = 0.80-0.93) (p0.001), with no systematic offset. The ultrasound variables decreased significantly (p0.001) with age in healthy women; the annual decrease was -0.4% for BUA, -0.07% for SOS, and -0.7% for SI. BUA, SOS and SI discriminated (p0.001) between fracture and non-fracture subjects, but the fracture groups were 2 to 4 yr older. The T-score in the controls averaged -2.1 while that in the fracture patients averaged about -3.0. After control for age, years since menopause, and body size, BUA, SOS as well as the SI remained significantly lower (11 to 12% for SI) in women with fracture. The Z-score was -0.8 (p0.01) in spine fracture cases, and -0.9 (p0.001) in hip fracture patients. QUS provides a gradient of fracture risk comparable to X-ray densitometry of the axial skeleton, and gives comparable Z- and T-scores in younger postmenopausal women. It provides a precise, radiation-free, low-cost, and rapid method for fracture risk assessment in clinical practice.

Objectives: To compare a composite ultrasonometry variable, the stiffness index (SI), with its two component variables of speed of sound (SOS) and broadband ultrasound attenuation (BUA), in identifying post-menopausal women with low bone mineral density (BMD) and/or osteoporotic fracture. Methods: A cross sectional sample of 1217 women (mean (S.D.) age 53.9 (9.7) years) was studied. Risk factors for osteoporosis were assessed by detailed questionnaire and women with diseases, or those taking treatments known to affect bone metabolism were excluded. Women were allocated to one of four groups: pre-menopausal women (n=476), healthy post-menopausal women (n=583), post-menopausal women with low BMD (n=101), and post-menopausal women with osteoporotic fracture (n=57). An Achilles ultrasonometer was used to perform quantitative ultrasonometry (QUS) at the os calcis. The SI, calculated mathematically from SOS and BUA, was computed. Results: Analysis of receiver operating curves (ROC) between healthy post-menopausal women and post-menopausal women with low BMD but no fracture, showed that the area under the curve (AUC) for SI was significantly greater than that for BUA (P

Background It is known that suboptimal adherence rates may affect endocrine treatments for breast cancer, but little information has been reported whether any efforts to improve treatment adherence have been successful. We designed a randomized, controlled study to investigate the effect of oral or written patient information program on adherence and persistence when receiving an aromatase inhibitor (AI). Methods The study cohort included 181 female patients receiving an adjuvant AI treatment randomly assigned to one of three groups. The first group received reminder letters and information booklets, the second group was reminded and informed through telephone calls and the control group received neither. The primary endpoint was the rate at which patients were classified as adhering to treatment after twelve months. Results Baseline results showed a well-balanced randomization with no significant differences between groups. After 12 months, 48% (CI 35–62) of the control group, 62.7% (CI 49–75) in the telephone group and 64.7% (CI 51–77) in the letter group were adhering to therapy. A post hoc pooled analysis with a one-way hypothesis for both interventions versus control indicated a significant difference between the groups favouring the intervention (p = 0.039). Conclusion The aim of this study was to investigate the efficacy of a simple and practical interventional program in enhancing adherence to breast cancer treatment. Patients receiving additional/supplemental information appeared to have an improved adherence rate even though the differences between groups were not statistically significant for the primary endpoint.

the aim of this study was to evaluate the influence of serum leptin concentration on bone mass assessed by quantitative ultrasound (QUS) in a large sample of healthy pre and postmenopausal women.555 healthy pre and postmenopausal (n=261 and n=294) women (mean age, 49.5+/-17.2 years) not on hormone replacement therapy were recruited on the occasion of a routine gynecological visit. Before entry to the study, all women had answered a detailed questionnaire on important risk factors and gave written informed consent. Speed of sound (SOS), broadband ultrasound attenuation (BUA) and stiffness index (SI) of the os Calcis were measured using the Achilles ultrasonometer (GE/lunar). We systematically investigated the relation of menopause, BMI and leptin on bone mass by allocating women into the following groups: (a) premenopausal women BMI25 kg/m(2) (N=178); (b) premenopausal women BMI25 kg/m(2) (N=83); (c) postmenopausal women BMI25 kg/m(2) (N=125); and (d) postmenopausal women BMI25 kg/m(2) (N=169). Additionally we investigated the relation of serum leptin concentrations, age and BMI on ultrasonometry variables by performing a multiple linear regression analyses.in the initial analyses premenopausal women showed a significantly (P0.001) lower mean age, weight, BMI, follicle stimulating hormone (FSH) and leptin concentration, a higher mean height, serum estradiol and ultrasonometry variables in comparison to postmenopausal women. Irrespective of the menopausal status, women with a BMI25 kg/m(2) had significantly higher leptin concentrations (P0.001) and BUA (P0.05) whereas SOS and SI was not significant different, compared to women with a BMI25 kg/m(2). The multiple linear regression analyses showed that only BMI but not Leptin was related to higher ultrasonometry variables, whereas increasing age was associated with a decrease in ultrasonometry variables. Furthermore, the multiple linear regression analyses confirmed that age and BMI were the only statistically significant independent predictor for ultrasonometry variables. There was no significant influence of leptin on ultrasonometry variables even after controlling for BMI or age, or BMI and age.serum leptin concentrations are significantly higher in pre and postmenopausal obese women, compared with normal weight controls. Ultrasonometry variables are influenced by age and BMI but not by serum leptin concentrations.

Reproductive factors such as parity and breast-feeding may be associated with low bone mass and osteoporotic fractures in later years. In this study, os calcis quantitative ultrasonometry was used to elucidate the relationship between parity, lactation and bone mass in postmenopausal women.This was a comparison study using subsequent matched pairs analysis as well as multiple linear regression analysis. The study was carried out at five centers in Germany. The study included 2,080 postmenopausal women (age (mean +/- SD) 58.8 +/- 8.2 years), who were attending for routine check-up and in whom diseases and drug treatments known to affect bone metabolism had been excluded.Women underwent quantitative ultrasonometry (QUS) measurement at the heel. Values of the ultrasonometry variables -speed of sound, broadband ultrasound attenuation and stiffness index -were calculated and compared for nulliparous and parous women and for women who had and had not breast-fed. Because of some significant intergroup differences, and to determine any effect of the number of live births and the duration of breast-feeding on ultrasonometry results, second analyses were undertaken using equally sized samples, matched for possible confounding variables such as age and body mass index (matched pairs). In these analyses, nulliparous women were compared with parous women, grouped according to number of live births, and women who had never breast-fed were compared with women who had breast-fed, grouped according to duration of breast-feeding. Furthermore, a multiple linear regression analysis was performed to examine the combined effects of reproductive factors on QUS variables.No statistically significant associations were found between ultrasonometry variables and parity or breast-feeding, even after controlling for confounding variables in matched-pairs analysis or in a multiple linear regression analysis.

OBJECTIVE: The aim of this study was to evaluate the influence of menopausal status, serum estradiol and body mass index (BMI) on serum leptin concentration in a large sample of pre- and postmenopausal women. DESIGN: 434 healthy women (mean age +/-s.d., 52.2 +/- 10.3 years) were recruited at the University of Marburg on the occasion of a routine gynecological visit. Two hundred and eighteen (50.2%) women were premenopausal (mean age, 36.5 +/- 10.4 years) and not on oral contraceptives or hormone replacement therapy (HRT) and 216 (49.8%) women were postmenopausal (mean age 61.8 +/- 8.9 years) not on HRT. To evaluate the influence of menopausal status, estradiol level and BMI on serum leptin concentrations, women were allocated to one of the four groups: (a) premenopausal women BMI 25 kg/m(2) (n=81), (c) postmenopausal women BMI 25 kg/m(2) (n=122). RESULTS: Irrespective of the menopausal status, women with a BMI >25 kg/m(2) had significantly higher leptin concentrations in all age groups compared with women with a BMI

OBJECTIVE: To evaluate the impact of long-term, non-suppressive levothyroxine (L-T(4)) treatment on quantitative ultrasonometry in women. DESIGN: This was a case-control study. SUBJECTS AND METHODS: Altogether 667 women (mean age+/-s.d., 49.5+/-13.1 years) were studied. Of these, 156 (23%) had non-toxic goitre or hypothyroidism and had been taking L-T(4) (75-100 microg/day) for at least 5 years (mean+/-s.d., 12.5+/-7.5 years); the remaining 511 (77%) women were not receiving L-T(4). All women had completed a questionnaire on risk factors for thyroid dysfunction and osteoporosis, and those with diseases or treatments known to effect bone metabolism - other than thyroxine or hormone replacement therapy (HRT) - were excluded. Women underwent quantitative ultrasonometry (QUS) at the heel. Speed of sound (SOS), broadband ultrasound attenuation (BUA) and the stiffness index (SI) were compared, first, in all women taking L-T(4) and controls and, secondly, in women taking L-T(4) and controls pair-matched for age, weight, body mass index (BMI), menopausal status and HRT use. RESULTS: Even after matching for age, weight, BMI, menopausal and HRT status, women taking L-T(4) had significantly lower values for SOS and SI (P

This study assessed age changes in quantitative ultrasound sonometry (QUS) in a large sample of healthy German women. Speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness index (SI) of the calcaneus were measured in 1333 women (mean age 50.5 +/- 11.5 years) using the Achilles ultrasonometer (Lunar Corp., Madison, WI, USA). The short-term precision in 31 adults was 0.2% for SOS, 1. 2% for BUA, and 1.3% for SI. There was an overall decline of 15% for BUA, 4% for SOS, and 31% for SI between late adolescence and old age. In premenopausal women, BUA decreased only slightly (-3%), whereas postmenopausal women showed a significantly increased decline (-12%). In contrast, SOS continuously decreased from the age of 15; there was a decline of 2% from adolescence to the menopause; postmenopausal women showed a slightly larger decline (-2.5%). The SI of premenopausal women decreased by 10%, but the postmenopausal decline of almost 22% was significantly greater. SI values for premenopausal German women were comparable to those observed in the American Achilles reference population, but postmenopausal German women had significantly higher SI values of 7% due to a lower rate of aging loss.