67 results on '"O. Hars"'
Search Results
2. Prevention of breast cancer treatment-induced bone loss in premenopausal women treated with zoledronic acid: Final 5-year results from the randomized, double-blind, placebo-controlled ProBONE II trial
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Friederike Thomasius, Peter H. Kann, Peyman Hadji, Ioannis Kyvernitakis, and O. Hars
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Adult ,medicine.medical_specialty ,Time Factors ,Histology ,Physiology ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Osteoporosis ,Urology ,Antineoplastic Agents ,Breast Neoplasms ,Placebo ,Zoledronic Acid ,Bone resorption ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Double-Blind Method ,medicine ,Humans ,Prospective Studies ,030212 general & internal medicine ,Bone Resorption ,Young adult ,Prospective cohort study ,Chemotherapy ,Bone Density Conservation Agents ,business.industry ,Middle Aged ,medicine.disease ,Treatment Outcome ,Zoledronic acid ,Premenopause ,030220 oncology & carcinogenesis ,Administration, Intravenous ,Drug Therapy, Combination ,Female ,business ,Follow-Up Studies ,medicine.drug - Abstract
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.
- Published
- 2018
3. Subjektive Erfahrung der Geburt von Müttern in West- und Ost-Berlin von 1950 – 1990 und 1990 – 2010: Analyse einer retrospektiven Umfrage
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O Hars, F Rupp, and Birgit Arabin
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- 2018
4. Quantitative ultrasonometry during pregnancy and lactation: a longitudinal study
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Jelena Boekhoff, J. Maier, C. Fischer, Lars Hellmeyer, B. Hahn, P. Hadji, and O. Hars
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Adult ,medicine.medical_specialty ,Bone density ,Endocrinology, Diabetes and Metabolism ,Osteoporosis ,Prenatal care ,Bone resorption ,Bone Density ,Pregnancy ,Lactation ,medicine ,Humans ,Longitudinal Studies ,Bone Resorption ,Ultrasonography ,business.industry ,Obstetrics ,Ultrasound ,medicine.disease ,Surgery ,Calcaneus ,medicine.anatomical_structure ,Female ,business - Abstract
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.
- Published
- 2014
5. Geburtserfahrung von Müttern in West- und Ost-Berlin von 1950 – 1990 und 1990 – 2010
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B Arabin, F Rupp, and O Hars
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- 2017
6. Subjektive Erfahrung von Schwangerschaft und Periode nach der Geburt von Müttern in West- und Ost-Berlin von 1950 – 1990 und 1990 – 2010
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J Grunewald, O Hars, B Arabin, and F Rupp
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- 2017
7. Influence of compliance on bone mineral density changes in postmenopausal women with early breast cancer on Anastrozole
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Matthias Kalder, O. Hars, Peyman Hadji, Dana Knöll, Volker Ziller, and Ioannis Kyvernitakis
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Oncology ,Receptors, Steroid ,Cancer Research ,medicine.medical_specialty ,Time Factors ,Bone density ,medicine.drug_class ,Osteoporosis ,Anastrozole ,Breast Neoplasms ,Absorptiometry, Photon ,Breast cancer ,Bone Density ,Internal medicine ,Nitriles ,medicine ,Humans ,Femur ,Aromatase ,Osteoporosis, Postmenopausal ,Aged ,Bone mineral ,Lumbar Vertebrae ,Aromatase inhibitor ,biology ,Aromatase Inhibitors ,business.industry ,General Medicine ,Middle Aged ,Triazoles ,medicine.disease ,Postmenopause ,Treatment Outcome ,Chemotherapy, Adjuvant ,biology.protein ,Patient Compliance ,Female ,business ,Hormone ,medicine.drug - Abstract
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.
- Published
- 2013
8. Pregnancy-associated transient osteoporosis of the hip: results of a case-control study
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Melitta Hahn, Peyman Hadji, O. Hars, Lars Hellmeyer, Ioannis Kyvernitakis, and Jelena Boekhoff
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Adult ,medicine.medical_specialty ,Pediatrics ,Population ,Osteoporosis ,030209 endocrinology & metabolism ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Germany ,medicine ,Humans ,Orthopedics and Sports Medicine ,education ,Retrospective Studies ,030222 orthopedics ,Hip fracture ,education.field_of_study ,business.industry ,Hip Fractures ,Case-control study ,medicine.disease ,Magnetic Resonance Imaging ,Pregnancy Complications ,Case-Control Studies ,Orthopedic surgery ,Physical therapy ,Etiology ,Transient osteoporosis ,Female ,business ,Osteoporotic Fractures - Abstract
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.
- Published
- 2016
9. Serum Osteocalcin and CTX-MMP Concentration in Young Exercising Thoroughbred Racehorses
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Olivier M. Lepage, Hélène Amory, Benoit Remy, Joseph Sulon, B Carstanjen, P Langlois, and O. Hars
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Male ,medicine.medical_specialty ,Osteocalcin ,Radioimmunoassay ,Matrix metalloproteinase ,Bone and Bones ,Collagen Type I ,Pathology and Forensic Medicine ,Bone remodeling ,N-terminal telopeptide ,Physical Conditioning, Animal ,Internal medicine ,medicine ,Animals ,Horses ,Prospective Studies ,General Veterinary ,biology ,business.industry ,Age Factors ,Matrix Metalloproteinases ,Endocrinology ,biology.protein ,Female ,Collagen ,Serum osteocalcin ,Peptides ,business ,Type I collagen ,Blood sampling - Abstract
Summary Bone responds to exercise with changes in bone (re-)modelling, which might be monitored non-invasively with biochemical bone markers. The aim of this study was to evaluate the influence of exercise on serum osteocalcin and serum carboxy-terminal cross-linked telopeptide of type I collagen generated by matrix metalloproteinases (CTX-MMP) concentration in young racehorses. Seventy-one 2 to 4-year-old Thoroughbreds were included in this prospective infield study. Blood sampling was performed six times (i.e. six sampling cycles) during a 9-month period. Serum samples were analysed with commercial osteocalcin and CTX-MMP radioimmunoassays. Two-year-old racehorses had higher serum osteocalcin and CTX-MMP values than 3-year-old horses. Gender and training amplitude did not significantly influence serum osteocalcin and CTX-MMP values. Two-year-old horses showed an increase in osteocalcin values between cycles 2 and 3 and an increase in serum CTX-MMP values between cycles 1 and 2. Serum osteocalcin and CTX-MMP concentrations decreased between cycles 4 and 5, and 5 and 6. Three-year-old horses showed an increase in serum osteocalcin levels between cycles 3 and 4 and an increase in serum CTX-MMP concentrations between cycles 1 and 2, and 3 and 4. Serum osteocalcin levels decreased between cycles 5 and 6, whereas serum CTX-MMP levels decreased between cycles 4 and 5, and 5 and 6. Two- and three-year-old horses showed a decreased osteocalcin/CTX-MMP ratio between cycles 1 and 2. Moreover, 2-year-old horses showed an increase in the osteocalcin/CTX-MMP ratio between cycles 2 and 3. Sore shin formation did not significantly influence serum osteocalcin and CTX-MMP values. Serum osteocalcin and CTX-MMP are promising bone markers for monitoring exercise induced changes in equine bone metabolism.
- Published
- 2005
10. Speed of sound measurements of the third metacarpal bone in young exercising thoroughbred racehorses
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B Carstanjen, Olivier M. Lepage, O. Hars, P Langlois, Hélène Amory, and François Duboeuf
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Male ,Dorsum ,Histology ,Physiology ,Endocrinology, Diabetes and Metabolism ,Physical Exertion ,Physical exercise ,Running ,Sex Factors ,Physical Conditioning, Animal ,medicine ,Animals ,Horses ,Longitudinal Studies ,Prospective Studies ,Ultrasonography ,Axial transmission ,business.industry ,Age Factors ,Horse ,Anatomy ,medicine.anatomical_structure ,Correlation analysis ,Third metacarpal bone ,Ultrasound imaging ,bacteria ,Female ,Cortical bone ,Metacarpus ,business - Abstract
The purpose of this longitudinal in-field study was to evaluate the influence of exercise, age, and gender on superficial cortical bone of the third metacarpal bone (MC III) in young Thoroughbreds by measuring speed of sound (SOS) values with an axial transmission technique (Omnisense, Sunlight Ltd, Israel). Both MC III of 75 racehorses, 2 to 4 years old, were monitored with SOS measurements in 5- to 7-week intervals during a 9- month physical exercise period. Medical data and training programs (slow gallop, canter, and high-speed work) of each horse were recorded. SOS measurements began before 2-year-old horses started high-speed training. SOS values of the dorsal aspect of MC III were significantly lower in comparison with values obtained at the lateral and the medial aspect of MC III, and SOS values were inversely correlated with measurement cycles. Significant limb-associated differences in dorsal MC III SOS values were observed at measurement cycles 2, 3, and 4. SOS values obtained at the lateral and medial aspect of MC III increased with age. SOS values obtained at the dorsal aspect of MC III, decreased with age. Mares had significantly higher SOS values at the dorsal aspect of MC III, when compared with corresponding values in stallions. In 2-year-old Thoroughbreds SOS values of the dorsal MC III were significantly different between cycles 1 and 2, between cycles 3 and 4, and between cycles 4 and 5. Three-year-old horses showed significant differences between SOS values of the dorsal MC III obtained at cycles 3 and 4. Training intensities did not significantly influence SOS values. The results indicate that young exercising Thoroughbred racehorses have age-, gender-, and measurement-cycle-dependent variations in SOS values of MC III, which probably reflect adaptive variations in superficial cortical bone properties of MC III.
- Published
- 2003
11. Age-Associated Changes in Bone Ultrasonometry of the os calcis
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Mathias Kalder, P. Hadji, May Gottschalk, J. Backhus, O. Hars, and Klaus-Dieter Schulz
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Adult ,Aging ,medicine.medical_specialty ,Adolescent ,Cross-sectional study ,Endocrinology, Diabetes and Metabolism ,Osteoporosis ,Reference Values ,Germany ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Orthopedics and Sports Medicine ,Aged ,Ultrasonography ,Aged, 80 and over ,Gynecology ,Age changes ,Postmenopausal women ,business.industry ,Middle Aged ,medicine.disease ,Late adolescence ,Large sample ,Menopause ,Calcaneus ,Cross-Sectional Studies ,Female ,business - Abstract
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.
- Published
- 2002
12. Influence of pregnancy and breast-feeding on quantitative ultrasonometry of bone in postmenopausal women
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M. Gottschalk, Stephan Schmidt, Matthias Kalder, Klaus-Dieter Schulz, P. Hadji, Volker Ziller, O. Hars, and Lars Hellmeyer
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Gynecology ,Pregnancy ,medicine.medical_specialty ,Postmenopausal women ,Heel ,business.industry ,Osteoporosis ,Obstetrics and Gynecology ,General Medicine ,medicine.disease ,Bone remodeling ,medicine.anatomical_structure ,medicine ,Parity (mathematics) ,business ,Breast feeding ,Bone mass - Abstract
Objective: 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. Design: 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 2080 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. Methods and outcome measures: 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. Bec...
- Published
- 2002
13. Effect of aromatase inhibition on serum levels of sclerostin and dickkopf-1, bone turnover markers and bone mineral density in women with breast cancer
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Ioannis Kyvernitakis, Peyman Hadji, Lorenz C. Hofbauer, Tilman D. Rachner, Anja Urbschat, and O. Hars
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musculoskeletal diseases ,Genetic Markers ,Cancer Research ,medicine.medical_specialty ,Time Factors ,Antineoplastic Agents ,Bone Neoplasms ,Breast Neoplasms ,Enzyme-Linked Immunosorbent Assay ,Osteocytes ,Bone remodeling ,chemistry.chemical_compound ,Breast cancer ,Osteoprotegerin ,Bone Density ,Internal medicine ,Biomarkers, Tumor ,Medicine ,Humans ,Prospective Studies ,Prospective cohort study ,Adaptor Proteins, Signal Transducing ,Aged ,Bone mineral ,Hematology ,business.industry ,Aromatase Inhibitors ,Wnt signaling pathway ,General Medicine ,Middle Aged ,medicine.disease ,Postmenopause ,Wnt Proteins ,Endocrinology ,Oncology ,chemistry ,Bone Morphogenetic Proteins ,Sclerostin ,Intercellular Signaling Peptides and Proteins ,Female ,Bone Remodeling ,business ,Follow-Up Studies - Abstract
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.
- Published
- 2014
14. Quantitative Ultrasonometrie (QUS) am Os calcaneus bei Frauen. Erstellung eines deutschen Referenzkollektives
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Matthias Kalder, P. Hadji, M. Gottschalk, M. Meyer-Wittkopf, K. Münstedt, Klaus-Dieter Schulz, and O. Hars
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medicine.medical_specialty ,Bone disease ,business.industry ,Coefficient of variation ,Attenuation ,Osteoporosis ,Ultrasound ,Obstetrics and Gynecology ,medicine.disease ,Surgery ,Menopause ,Speed of sound ,Maternity and Midwifery ,medicine ,Calcaneus ,business ,Nuclear medicine - Abstract
Objective: Quantitative ultrasonometry is a radiation-free, low-cost, simple, quick and mobile method to evaluate properties of bone. The objective of this study was to evaluate the effectiveness, reliability and age-related findings of this technique in women and to establish a reference database. Methods: In a cross-sectional study we measured speed of sound, broadband ultrasound attenuation and the stiffness index of the calcaneus in 2272 women (mean age, 53.0 ± 10.5 years) with an ultrasound bone densitometer. Women with a history of osteoporosis, osteoporosis-related fractures or those using medications known to affect bone metabolism were excluded. In 791 women both calcanei were studied. Results: The short-term precision in vivo, expressed as coefficient of variance, was 1.2% for broadband attenuation, 0.2% for speed of sound, and 1.3% for stiffness. In women in whom both calcanei were studied the coefficient of correlation was 0.92 for speed of sound (p
- Published
- 2001
15. Quantitative Ultrasonometrie am Calcaneus zur Abschätzung der Knochendichte in Schwangerschaft und Stillzeit
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C. Fischer, Lars Hellmeyer, M Hahn, O. Hars, B. Hahn, J Boekhoff, and Peyman Hadji
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Maternity and Midwifery ,Pediatrics, Perinatology and Child Health ,Obstetrics and Gynecology - Published
- 2013
16. The influence of hormone replacement therapy (HRT) on serum leptin concentration in postmenopausal women
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Peyman Hadji, G. Emons, Thomas Bauer, Klaus-Dieter Schulz, O. Hars, and Kay Görke
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Leptin ,medicine.medical_specialty ,Hormone Replacement Therapy ,medicine.drug_class ,General Biochemistry, Genetics and Molecular Biology ,Body Mass Index ,Age Distribution ,Internal medicine ,medicine ,Humans ,Obesity ,Postmenopausal women ,Estradiol ,business.industry ,Obstetrics and Gynecology ,Estrogens ,Middle Aged ,medicine.disease ,Postmenopause ,Menopause ,Endocrinology ,Transgender hormone therapy ,Estrogen ,Serum leptin ,Female ,Follicle Stimulating Hormone ,Progestins ,business ,Body mass index - Abstract
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.
- Published
- 2000
17. Quantitative Ultrasound of Os Calcis in Postmenopausal Women with Spine and Hip Fractures
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O. Hars, K. Görke, Klaus D. Schulz, Peyman Hadji, and Günther Emons
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musculoskeletal diseases ,medicine.medical_specialty ,Heel ,Endocrinology, Diabetes and Metabolism ,Osteoporosis ,Stiffness index ,Bone Density ,Predictive Value of Tests ,Risk Factors ,Surveys and Questionnaires ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Orthopedics and Sports Medicine ,Osteoporosis, Postmenopausal ,Aged ,Ultrasonography ,Spine fracture ,Analysis of Variance ,Hip fracture ,Postmenopausal women ,Hip Fractures ,business.industry ,Ultrasound ,Middle Aged ,medicine.disease ,Quantitative ultrasound ,Calcaneus ,medicine.anatomical_structure ,Spinal Fractures ,Female ,Radiology ,business - Abstract
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.
- Published
- 2000
18. Knochendichte bei Patientinnen mit Mammakarzinom im Vergleich zu gesunden matched-pair Kontrollen
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A. Spiess, C. Jäckel, G. Emons, P. Hadji, Karin Bock, Klaus-Dieter Schulz, U.-S. Albert, and O. Hars
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Oncology ,Bone mineral ,medicine.medical_specialty ,Bone disease ,business.industry ,Osteoporosis ,Obstetrics and Gynecology ,medicine.disease ,Lower risk ,Endocrinology ,Breast cancer ,Internal medicine ,Maternity and Midwifery ,medicine ,Risk factor ,skin and connective tissue diseases ,business ,Breast feeding ,Body mass index - Abstract
Objective: Because estrogens are important in the pathogenesis of both breast cancer and osteoporosis, it has been suggested that the risk of osteoporosis and breast cancer are inversely related. The aim of our study was to evaluate bone mineral density in patients with breast cancer. Methods: Speed of sound, broadband ultrasound attenuation, and the stiffness index of the calcaneus were measured in 1004 subjects (mean age 53.9 years) with an Achilles ultrasound bone densitometer. 148 patients had a history of breast cancer and 856 did not. Breast cancer patients were compared with healthy subjects matched for age, weight, body mass index (BMI), parity, and duration of breast feeding and estrogen exposure. Results: Overall, the patients with breast cancer were 4.4 years older and had higher body weight, BMI and parity, longer duration of breast feeding and estrogen exposure, and a significantly higher speed of sound and stiffness index than healthy controls. In the matched-pairs analysis, women with breast cancer had a higher speed of sound and stiffness index than the controls. Conclusion: Women with breast cancer have a lower risk of osteoporosis than controls. Although the biologic mechanisms linking bone mass and the risk of breast cancer are not fully understood, factors other than cumulative estrogen exposure may play a role. Studies on larger populations are needed to evaluate this relationship.
- Published
- 1999
19. Stiffness index identifies patients with osteoporotic fractures better than ultrasound velocity or attenuation alone
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Karin Bock, Peyman Hadji, Chr. Wüster, U.-S. Alberts, O. Hars, H.-G. Bohnet, Klaus-Dieter Schulz, and G. Emons
- Subjects
musculoskeletal diseases ,medicine.medical_specialty ,Bone density ,Bone disease ,Cross-sectional study ,Osteoporosis ,Urology ,General Biochemistry, Genetics and Molecular Biology ,Bone remodeling ,Bone Density ,Risk Factors ,Humans ,Medicine ,Osteoporosis, Postmenopausal ,Retrospective Studies ,Ultrasonography ,Bone mineral ,business.industry ,Ultrasound ,Area under the curve ,Obstetrics and Gynecology ,Middle Aged ,medicine.disease ,Surgery ,Cross-Sectional Studies ,Fractures, Spontaneous ,ROC Curve ,Female ,business - Abstract
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
- Published
- 1999
20. Persistency with estrogen replacement therapy among hysterectomized women after the Women’s Health Initiative study
- Author
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I. Kyvernitakis, K. Kostev, O. Hars, U-s. Albert, M. Kalder, P. Hadji, I. Kyvernitakis, K. Kostev, O. Hars, U-s. Albert, M. Kalder, and P. Hadji
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- 2015
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21. Discontinuation rates of menopausal hormone therapy among postmenopausal women in the post-WHI study era
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I. Kyvernitakis, K. Kostev, O. Hars, U-s. Albert, P. Hadji, I. Kyvernitakis, K. Kostev, O. Hars, U-s. Albert, and P. Hadji
- Published
- 2015
- Full Text
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22. Quantitative Ultraschallsonographie (QUS) am Os calcaneus bei postmenopausalen Frauen
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G. Emons, O. Hars, H.-G. Bohnet, Klaus-Dieter Schulz, and P. Hadji
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medicine.medical_specialty ,Bone disease ,business.industry ,Coefficient of variation ,Osteoporosis ,Ultrasound ,Obstetrics and Gynecology ,medicine.disease ,Bone remodeling ,Surgery ,Quantitative ultrasound ,Maternity and Midwifery ,medicine ,Densitometer ,Calcaneus ,business ,Nuclear medicine - Abstract
Purpose: This cross-sectional study collected data on the effectiveness, validity and reliability of QUS. Method and Material: Speed of sound (SOS), broadband ultrasound attenuation (BUA) and stiffness index (SI) of the calcaneus were measured in n = 764 postmenopausal patients, mean age 61 years, using the Achilles ultrasound bone densitometer (Lunar Corp., Madison, WI). In addition we measured blood levels of E2 and FSH in 157 patients and correlated these variables with data gathered by a detailed questionnaire. Women using any medication known to effect bone metabolism were excluded from the study. Results: The Achilles shortterm precision in vivo expressed as coefficient of variance was 1.2 % for BUA and 0.17% for SOS and 1.3% for stiffness respectively. A total of 102 women were measured at the right and left calcaneus with a coefficient of correlation of r= 0.92 for SOS, r = 0.84 for BUA and r = 0.93 for SI. Cross-sectional analysis showed a significant yearly postmenopausal decrease of 0.06% for SOS, 0.44% for BUA and 0.74% for SI. Women with a history of osteoporosis (165 patients) as well as 141 women with an osteoporosis-related fracture showed significantly lower results in all ultrasound parameters (SOS, BUA, SI). In conclusion, quantitative ultrasound osteodensitometry of the calcaneus measures properties of bone which continue to decline with age. The low precision error and the high correlation of right vs. left underlines the high technical standard. Conclusion: Our results indicate that QUS is capable of identifying in a precise manner women with previous osteoporotic fractures as well as women with a history of osteoporosis. Hence, QUS may provide a radiation-free, low-cost, easy to handle, fast and mobile method which for the first time could make a screening programme a feasible proposition.
- Published
- 1998
23. Influence of a patient information program on adherence and persistence with an aromatase inhibitor in breast cancer treatment--the COMPAS study
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Peyman Hadji, Astrid Storch, O. Hars, Dana Knöll, Volker Ziller, and Ioannis Kyvernitakis
- Subjects
Cancer Research ,medicine.medical_specialty ,Randomization ,Antineoplastic Agents, Hormonal ,medicine.drug_class ,Endocrine treatment ,Psychological intervention ,Breast Neoplasms ,law.invention ,Medication Adherence ,Breast cancer ,Randomized controlled trial ,Patient Education as Topic ,law ,Internal medicine ,Genetics ,Clinical endpoint ,Medicine ,Humans ,Aged ,Neoplasm Staging ,Aromatase inhibitor ,business.industry ,Aromatase Inhibitors ,Middle Aged ,medicine.disease ,Combined Modality Therapy ,Clinical trial ,Treatment Outcome ,Oncology ,Adherence ,Cohort ,Physical therapy ,Female ,business ,Research Article ,Compliance - Abstract
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.
- Published
- 2013
24. The influence of serum leptin concentration on bone mass assessed by quantitative ultrasonometry in pre and postmenopausal women
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M Gotschalk, G Emons, P. Hadji, Karin Bock, O. Hars, Klaus-Dieter Schulz, and J. Backhus
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Adult ,Leptin ,medicine.medical_specialty ,Bone disease ,medicine.medical_treatment ,Osteoporosis ,General Biochemistry, Genetics and Molecular Biology ,Body Mass Index ,Bone Density ,Internal medicine ,Germany ,Surveys and Questionnaires ,Linear regression ,medicine ,Humans ,Osteoporosis, Postmenopausal ,Aged ,Ultrasonography ,Aged, 80 and over ,Estradiol ,business.industry ,Age Factors ,Obstetrics and Gynecology ,Hormone replacement therapy (menopause) ,Middle Aged ,medicine.disease ,Obesity ,Menopause ,Endocrinology ,Regression Analysis ,Female ,business ,Body mass index - Abstract
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.
- Published
- 2003
25. Influence of pregnancy and breast-feeding on quantitative ultrasonometry of bone in postmenopausal women
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P, Hadji, V, Ziller, M, Kalder, M, Gottschalk, L, Hellmeyer, O, Hars, S, Schmidt, and K-D, Schulz
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Adult ,Aged, 80 and over ,Middle Aged ,Parity ,Bone Density ,Pregnancy ,Case-Control Studies ,Germany ,Surveys and Questionnaires ,Humans ,Lactation ,Regression Analysis ,Female ,Osteoporosis, Postmenopausal ,Aged ,Ultrasonography - Abstract
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.
- Published
- 2002
26. The influence of menopause and body mass index on serum leptin concentrations
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T Bauer, P. Hadji, Klaus-Dieter Schulz, Karin Bock, G. Emons, G Sturm, and O. Hars
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Adult ,Leptin ,medicine.medical_specialty ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Body Mass Index ,Endocrinology ,Internal medicine ,Blood plasma ,medicine ,Humans ,Aged ,Estradiol ,business.industry ,Hormone replacement therapy (menopause) ,General Medicine ,Middle Aged ,medicine.disease ,Obesity ,Menopause ,Blood chemistry ,Estrogen ,Linear Models ,Female ,Follicle Stimulating Hormone ,business ,Body mass index - Abstract
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
- Published
- 2000
27. The effect of long-term, non-suppressive levothyroxine treatment on quantitative ultrasonometry of bone in women
- Author
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G. Emons, O. Hars, T Bauer, G Sturm, Peyman Hadji, and Klaus-Dieter Schulz
- Subjects
Adult ,medicine.medical_specialty ,Thyroid Hormones ,Time Factors ,Bone disease ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Osteoporosis ,Levothyroxine ,Bone and Bones ,Bone remodeling ,Endocrinology ,Hypothyroidism ,Risk Factors ,Internal medicine ,Surveys and Questionnaires ,medicine ,Humans ,Aged ,Ultrasonography ,Aged, 80 and over ,business.industry ,Goiter ,Case-control study ,Hormone replacement therapy (menopause) ,General Medicine ,Middle Aged ,medicine.disease ,Menopause ,Calcaneus ,Thyroxine ,Case-Control Studies ,Female ,business ,Body mass index ,medicine.drug - Abstract
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
- Published
- 2000
28. Age changes of calcaneal ultrasonometry in healthy German women
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M. W. Beckmann, Klaus-Dieter Schulz, P. Hadji, G. Emons, O. Hars, Karin Bock, and U.-S. Albert
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Adult ,medicine.medical_specialty ,Aging ,Bone density ,Adolescent ,Cross-sectional study ,Endocrinology, Diabetes and Metabolism ,Osteoporosis ,Endocrinology ,Bone Density ,Germany ,medicine ,Humans ,Orthopedics and Sports Medicine ,Osteoporosis, Postmenopausal ,Aged ,Ultrasonography ,Gynecology ,Aged, 80 and over ,Age changes ,business.industry ,Reproducibility of Results ,Middle Aged ,medicine.disease ,Late adolescence ,Menopause ,Quantitative ultrasound ,Calcaneus ,Cross-Sectional Studies ,Premenopause ,Body Constitution ,Female ,business - Abstract
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.
- Published
- 1999
29. 5 SPEED OF SOUND MEASUREMENTS OF THE THIRD METACARPAL BONE IN EXERCISING THOROUGHBRED RACEHORSES
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O. Hars, B Carstanjen, Hélène Amory, OM Lepage, and P Langlois
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Orthodontics ,General Veterinary ,business.industry ,Speed of sound ,Third metacarpal bone ,Medicine ,business - Published
- 2003
30. Blue light excited retinal intercepts cellular signaling
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Kasun Ratnayake, John L. Payton, O. Harshana Lakmal, and Ajith Karunarathne
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Medicine ,Science - Abstract
Abstract Photoreceptor chromophore, 11-cis retinal (11CR) and the photoproduct, all-trans retinal (ATR), are present in the retina at higher concentrations and interact with the visual cells. Non-visual cells in the body are also exposed to retinal that enters the circulation. Although the cornea and the lens of the eye are transparent to the blue light region where retinal can absorb and undergo excitation, the reported phototoxicity in the eye has been assigned to lipophilic non-degradable materials known as lipofuscins, which also includes retinal condensation products. The possibility of blue light excited retinal interacting with cells; intercepting signaling in the presence or absence of light has not been explored. Using live cell imaging and optogenetic signaling control, we uncovered that blue light-excited ATR and 11CR irreversibly change/distort plasma membrane (PM) bound phospholipid; phosphatidylinositol 4,5 bisphosphate (PIP2) and disrupt its function. This distortion in PIP2 was independent of visual or non-visual G-protein coupled receptor activation. The change in PIP2 was followed by an increase in the cytosolic calcium, excessive cell shape change, and cell death. Blue light alone or retinal alone did not perturb PIP2 or elicit cytosolic calcium increase. Our data also suggest that photoexcited retinal-induced PIP2 distortion and subsequent oxidative damage incur in the core of the PM. These findings suggest that retinal exerts light sensitivity to both photoreceptor and non-photoreceptor cells, and intercepts crucial signaling events, altering the cellular fate.
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- 2018
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31. P-11. Age-Related Changes in Quantitative Ultrasound Sonography (QUS) in Healthy German Women
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G. Emons, P. Hadji, K. D. Schulz, and O. Hars
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Quantitative ultrasound ,German ,medicine.medical_specialty ,business.industry ,Obstetrics ,Age related ,language ,Obstetrics and Gynecology ,Medicine ,business ,language.human_language - Published
- 1998
32. P-9. Is Quantitative Ultrasound Sonography (QUS) Able to Identify Osteoporosis in Postmenopausal Women?
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Karin Bock, O. Hars, P. Hadji, G. Emons, and K. D. Schulz
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Quantitative ultrasound ,medicine.medical_specialty ,Postmenopausal women ,Obstetrics ,business.industry ,Osteoporosis ,medicine ,Obstetrics and Gynecology ,medicine.disease ,business - Published
- 1998
33. P-10. Stiffness Index Identifies Osteoporotic Fracture Better than Broadband Ultrasound Attenuation (BUA) or Speed of Sound (SOS) Alone
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P. Hadji, K. D. Schulz, and O. Hars
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Broadband ultrasound attenuation ,business.industry ,Acoustics ,Speed of sound ,Obstetrics and Gynecology ,Medicine ,Stiffness index ,Osteoporotic fracture ,business - Published
- 1998
34. Correction to: Subsequent fracture risk of women with pregnancy and lactation-associated osteoporosis after a median of 6 years of follow-up.
- Author
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Kyvernitakis I, Reuter TC, Hellmeyer L, Hars O, and Hadji P
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- 2023
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35. In Early Breast Cancer, the Ratios of Neutrophils, Platelets and Monocytes to Lymphocytes Significantly Correlate with the Presence of Subsets of Circulating Tumor Cells but Not with Disseminated Tumor Cells.
- Author
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Kasimir-Bauer S, Karaaslan E, Hars O, Hoffmann O, and Kimmig R
- Abstract
Circulating tumor cells (CTCs) crosstalk with different blood cells before a few of them settle down as disseminated tumor cells (DTCs). We evaluated the correlation between CTC subtypes, DTCs and the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and monocyte to lymphocyte ratio (MLR) for better prognostication of 171 early staged diagnosed breast cancer (BC) patients. -Clinical data and blood values before treatment were retrospectively recorded, representing the 75% percentile, resulting in 3.13 for NLR, 222.3 for PLR and 0.39 for MLR, respectively. DTCs were analyzed by immunocytochemistry using the pan-cytokeratin antibodyA45-B/B3. CTCs were determined applying the AdnaTests BreastCancerDetect and EMT (Epithelial Mesenchymal Transition) Detect . -Reduced lymphocyte ( p = 0.007) and monocyte counts ( p = 0.012), an elevated NLR ( p = 0.003) and PLR ( p = 0.001) significantly correlated with the presence of epithelial CTCs while a reduced MLR was related to EMT-CTCs ( p = 0.045). PLR ( p = 0.029) and MLR ( p = 0.041) significantly related to lymph node involvement and monocyte counts significantly correlated with OS ( p = 0.034). No correlations were found for NLR, PLR and MLR with DTCs, however, DTC-positive patients, harboring a lower PLR, had a significant shorter OS ( p = 0.043). -Pro-inflammatory markers are closely related to different CTC subsets. This knowledge might improve risk prognostication of these patients.
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- 2022
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36. Clinical experience with misoprostol vaginal insert for induction of labor: a prospective clinical observational study.
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Schmidt M, Neophytou M, Hars O, Freudenberg J, and Kühnert M
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- Administration, Intravaginal, Adult, Cardiotocography, Cervix Uteri drug effects, Cesarean Section, Delivery, Obstetric, Female, Humans, Infant, Newborn, Misoprostol pharmacology, Oxytocics pharmacology, Pregnancy, Prospective Studies, Time Factors, Treatment Outcome, Young Adult, Labor, Induced, Labor, Obstetric drug effects, Misoprostol administration & dosage, Oxytocics administration & dosage
- Abstract
Purpose: To provide real-world evidence using misoprostol vaginal insert (MVI) for induction of labor in nulliparous and parous women at two German Level I Centers in a prospective observational study., Methods: Between 1 August 2014 and 1 October 2015, eligible pregnant women (≥ 36 + 0 weeks of gestation) requiring labor induction were treated with MVI. Endpoints included time to and mode of delivery rates of tocolysis use, tachysystole, uterine hypertonus or uterine hyperstimulation syndrome and newborn outcomes., Results: Of the 354 women enrolled, 68.9% (244/354) achieved vaginal delivery (nulliparous, 139/232 [59.9%]; parous 105/122 [86.1%]; p < 0.001). Median time from MVI administration to vaginal delivery was 14.0 h (nulliparous, 14.5 h; parous, 11.9 h; p < 0.001). A total of 205/244 (84.0%) and 228/244 (93.4%) women achieved a vaginal delivery within 24 h and 30 h, respectively. The most common indications for cesarean delivery were pathologic cardiotocography (nulliparous, 41/232 [17.4%]; parous, 13/122 [10.7%]; p = 0.081) and arrested labor (dilation or descent; nulliparous, 45/232 [19.4%], parous, 3/122 [2.5%]; p ≤ 0.001). A total of 24.3% of women experienced uterine tachysystole and 9.6% experienced uterine tachysystole with fetal heart rate involvement, neither of which were significantly different for nulliparous and parous women. In total, 42/345 (12.2%) of the neonates had an arterial pH < 7.15 and 12/345 3.5% had a 5-min Apgar score ≤ 7., Conclusion: When clinically indicated, MVI was efficient and safe for induction of labor in women with an unfavorable cervix. Women, however, should be counseled regarding the risk of uterine tachysystole prior to labor induction with MVI.
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- 2019
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37. Prevention of breast cancer treatment-induced bone loss in premenopausal women treated with zoledronic acid: Final 5-year results from the randomized, double-blind, placebo-controlled ProBONE II trial.
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Kyvernitakis I, Kann PH, Thomasius F, Hars O, and Hadji P
- Subjects
- Administration, Intravenous, Adult, Antineoplastic Agents administration & dosage, Bone Resorption chemically induced, Bone Resorption diagnostic imaging, Bone Resorption epidemiology, Breast Neoplasms diagnostic imaging, Breast Neoplasms epidemiology, Double-Blind Method, Drug Therapy, Combination, Female, Follow-Up Studies, Humans, Middle Aged, Premenopause physiology, Prospective Studies, Time Factors, Treatment Outcome, Young Adult, Antineoplastic Agents adverse effects, Bone Density Conservation Agents administration & dosage, Bone Resorption prevention & control, Breast Neoplasms drug therapy, Premenopause drug effects, Zoledronic Acid administration & dosage
- Abstract
Purpose: 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., Methods: 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., Results: 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., Conclusions: 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., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2018
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38. Subsequent fracture risk of women with pregnancy and lactation-associated osteoporosis after a median of 6 years of follow-up.
- Author
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Kyvernitakis I, Reuter TC, Hellmeyer L, Hars O, and Hadji P
- Subjects
- Aged, Anthropometry methods, Bone Density physiology, Bone Density Conservation Agents therapeutic use, Female, Follow-Up Studies, Humans, Middle Aged, Osteoporosis drug therapy, Osteoporosis physiopathology, Osteoporotic Fractures physiopathology, Osteoporotic Fractures prevention & control, Pregnancy, Recurrence, Risk Assessment methods, Spinal Fractures etiology, Spinal Fractures physiopathology, Lactation physiology, Osteoporosis etiology, Osteoporotic Fractures etiology, Pregnancy Complications
- Abstract
Almost a quarter of patients with PAO will sustain a subsequent fracture; patients need to be informed about potential risks before deciding for further pregnancies., Introduction: Pregnancy and lactation-associated osteoporosis (PAO) is a severe type of premenopausal osteoporosis which predominantly occurs in the last trimester of pregnancy or immediately postpartum. Long-term follow-up data including subsequent fracture risk have yet to be reported., Methods: This single-center prospective cohort study investigated the subsequent fracture risk of all 107 patients with PAO who were referred to our institution., Results: Overall, 107 presented with at least one fracture. Each patient sustained on average four fractures most commonly at the thoracolumbar spine. During a median of 6 years of follow-up, 26 (24.3%) of patients who had a fracture at baseline reported a subsequent fracture. Overall, 30 PAO patients (28%) reported a further pregnancy. In subsequent pregnancies, 6 (20%) of patients reported a subsequent fracture. Patients with up to 1 vs. > 1 fracture at time of diagnosis showed a 3 (10%) and 25 (27%) subsequent fracture rate, respectively (p = 0.047). There was a significant correlation between the number of fractures at time of diagnosis and subsequent fracture risk (N = 26,p= 0.56, p = 0.003)., Conclusions: Almost a quarter of patients with PAO will sustain a subsequent fracture, and this fracture risk correlates with the number of fractures at time of diagnosis. Patients with PAO need to be informed about their potential subsequent fracture risk before deciding for further pregnancies.
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- 2018
- Full Text
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39. Pregnancy-associated transient osteoporosis of the hip: results of a case-control study.
- Author
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Hadji P, Boekhoff J, Hahn M, Hellmeyer L, Hars O, and Kyvernitakis I
- Subjects
- Adult, Case-Control Studies, Female, Germany epidemiology, Humans, Magnetic Resonance Imaging methods, Pregnancy, Retrospective Studies, Hip Fractures epidemiology, Hip Fractures etiology, Hip Fractures prevention & control, Osteoporosis diagnosis, Osteoporosis epidemiology, Osteoporosis etiology, Osteoporosis physiopathology, Osteoporotic Fractures epidemiology, Osteoporotic Fractures etiology, Osteoporotic Fractures prevention & control, Pregnancy Complications diagnosis, Pregnancy Complications epidemiology, Pregnancy Complications physiopathology, Pregnancy Complications prevention & control
- Abstract
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., Introduction: 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., Methods: 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., Results: 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)., Conclusions: 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.
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- 2017
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40. Pregnancy-associated osteoporosis: a case-control study.
- Author
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Hadji P, Boekhoff J, Hahn M, Hellmeyer L, Hars O, and Kyvernitakis I
- Subjects
- Adult, Anthropometry methods, Case-Control Studies, Female, Germany epidemiology, Humans, Middle Aged, Osteoporosis epidemiology, Osteoporotic Fractures epidemiology, Osteoporotic Fractures etiology, Pregnancy, Risk Factors, Young Adult, Osteoporosis etiology, Pregnancy Complications epidemiology
- Abstract
The etiology and underlying mechanisms of pregnancy-associated osteoporosis (PAO) are still unknown, since no systematic analyses exist. Our results indicate that PAO is a heterogeneous, rare but severe disease including a substantial number of fractures with a significant delay from first symptom to diagnose., Introduction: Pregnancy-associated osteoporosis (PAO) is a rare but severe type of premenopausal osteoporosis. Most common symptom includes acute lower back pain due to vertebral fracture predominantly occurring in the last trimester of pregnancy or immediately postpartum. The exact underlining mechanisms and risk factors of PAO are still unknown, and up to date, there are no published systematic analyses., Methods: We identified 102 PAO patients and matched them with 102 healthy controls according to age, region, and gravidity to evaluate risk factors in a large and homogenous population of women., Results: The baseline characteristics and anthropometric data of the two study groups were similar. Eighty-eight percent of the patients with PAO suffered from one or more fractures with a mean of 3.3 fractures per patient. The most common fracture site was the thoracolumbar spine, whereas 29, 37, 48, and 35% of the patients reported fractures at TH11, TH12, L1, and L2, respectively. PAO patients suffered more frequently from excessive dental problems in childhood (p < 0.001). The control group performed significantly more frequently sports both before (p < 0.002) and after puberty (p < 0.01). Compared to the controls, the patients with PAO reported twice as often severe diseases during pregnancy (p < 0.029). Hereby, the frequency of immobilization was twice as often in the PAO group compared to that in the control group (p < 0.005)., Conclusions: Our results indicate that PAO is a heterogeneous, rare but severe disease including a substantial number of fractures with a significant delay from first symptom to diagnose. Increased awareness is warranted to immediately start effective treatment.
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- 2017
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41. Comparison of combined low-dose hormone therapy vs. tibolone in the prevention of bone loss.
- Author
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Kalder M, Kyvernitakis I, Hars O, Kauka A, and Hadji P
- Subjects
- Absorptiometry, Photon, Bone Density drug effects, Estradiol adverse effects, Estrogen Replacement Therapy, Female, Humans, Middle Aged, Norethindrone adverse effects, Norpregnenes adverse effects, Prospective Studies, Uterine Hemorrhage etiology, Estradiol administration & dosage, Norethindrone administration & dosage, Norpregnenes administration & dosage, Osteoporosis, Postmenopausal prevention & control
- Abstract
Objectives: To compare the effects on bone mineral density (BMD) measured by dual-energy X-ray absorptiometry at the lumbar spine, the femoral neck and the total hip following 2 years of treatment with a low-dose combined hormone therapy (HT) comprised of 1 mg estradiol and 0.5 mg norethisterone acetate (E2/NETA) versus 2.5 mg tibolone in postmenopausal women. Additionally, quantitative ultrasonometry (QUS) of the os calcaneus and of the phalanges was performed., Methods: Changes in BMD, QUS and side-effects were assessed at baseline, 6, 12 and 24 months in 50 postmenopausal women who received either E2/NETA (n = 26) or tibolone (n = 24) for 2 years., Results: Compared to women on tibolone, women receiving E2/NETA showed a significant increase in BMD from baseline to 12 and 24 months at the lumbar spine (3.07%, 3.86%; p < 0.01 vs. 1.13%, 2.23%; p < 0.05), and at the total hip (1.33%, 1.69%; p < 0.01 vs. 0.76%, 0.70%) and at the femoral neck from baseline to 24 months (1.10%; p < 0.05). QUS indices only showed a significant change with the ultrasound bone profile index with E2/NETA at 6 months (-2.32%; p < 0.001)., Conclusions: Low-dose E2/NETA showed a significantly higher increase in BMD compared to tibolone. QUS measurement was not considered to comprise beneficial effects in monitoring drug-induced bone changes.
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- 2016
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42. Discontinuation rates of menopausal hormone therapy among postmenopausal women in the post-WHI study era.
- Author
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Kyvernitakis I, Kostev K, Hars O, Albert US, and Hadji P
- Subjects
- Adult, Clinical Trials as Topic, Female, Humans, Middle Aged, Estrogen Replacement Therapy statistics & numerical data, Estrogens administration & dosage, Medication Adherence statistics & numerical data, Women's Health statistics & numerical data
- Abstract
Objectives: Many women are reluctant to take menopausal hormone therapy (MHT) and discontinue the treatment within 12 months. The aim of this study was to investigate the persistence rates of combined MHT in the last decade, reflecting changes in the post-Women's Health Initiative era., Methods: We analyzed 17 020 patients receiving combined MHT from 2004 to 2013 using the Disease Analyzer database., Results: After 12 months of follow-up, 44.6% and 33.5% of patients receiving 1 mg and 2 mg, respectively, of oral combined MHT were still on treatment (p < 0.0001). The persistence rate of patients receiving < 50 μg of transdermal MHT was 39.1% after 1 year of treatment and presented no differences compared to patients receiving ≥ 50 μg of transdermal MHT with a persistence rate of 38.2%. MHT start in the years 2007-2009 was associated with higher discontinuation rates (hazard ratio 1.04, p = 0.0709) than MHT start in the years 2010-2013 (hazard ratio 0.90, p = 0.0001)., Conclusions: Our results indicate that patients beginning their treatments in the years 2010-2013 were more treatment-persistent than patients beginning with MHT in the early years after publication of the Women's Health Initiative study (2004-2009). Administration of low-dose oral MHT and transdermal MHT is associated with increased persistency compared to higher doses of oral MHT.
- Published
- 2015
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43. Comparison of dual-energy X-ray absorptiometry with six quantitative ultrasonometry devices in women with hip fractures.
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Hadji P, Imani P, Wüster C, Hars O, Albert US, and Kyvernitakis I
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- Aged, Aged, 80 and over, Female, Humans, Odds Ratio, Postmenopause, Prognosis, Risk Assessment, Risk Factors, Ultrasonography instrumentation, Absorptiometry, Photon methods, Bone Density, Hip Fractures diagnostic imaging, Osteoporotic Fractures complications, Ultrasonography methods
- Abstract
Objectives: Dual-energy X-ray absorptiometry (DXA) is the gold standard for assessment of bone mineral density, an important risk factor for osteoporotic fractures. Recent reports suggest that quantitative ultrasonometry (QUS) is able to predict fractures; however, only limited data in women with hip fractures are available., Methods: We examined 91 postmenopausal women who had sustained an osteoporosis-related hip fracture within the past 7 days using DXA and six different QUS devices and compared them with 91 healthy age-matched controls., Results: Femoral neck (FN), total hip (TH) and lumbar spine (LS) T-scores were lower in women with hip fractures compared to matched controls: - 2.38 vs. - 1.64 (p < 0.001), - 2.36 vs. - 1.44 (p < 0.001) and - 2.05 vs. - 1.50 (p = 0.41), respectively. The T-scores of the Achilles, Sahara, InSight and Omnisence QUS devices were also lower in patients with hip fractures compared to matched controls: - 3.20 vs. - 2.36 (p < 0.001), - 2.196 vs. - 1.761 (p = 0.005), - 2.631 vs. - 1.849 (p < 0.001), - 3.707 vs. - 3.030 (p = 0.032), respectively. However, the T-scores of the DBM and QUS-2 did not differ between the two groups: - 4.543 vs. - 4.324 (p = 0.352) and - 1.7 vs. - 2.0 (p = 0.465), respectively. Compared to DXA (hip), the odds ratios of the Achilles, InSight and Sahara were comparable, while the odds ratios of the DBM, Omnisence and QUS-2 were significantly lower (p ≤ 0.05)., Conclusions: Compared to DXA, the Achilles, Sahara and InSight QUS devices showed similar hip fracture discrimination while the DBM, Omnisence and QUS-2 did not. Therefore, some QUS devices are able to identify a clinically meaningful risk factor in women at high risk of hip fracture.
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- 2015
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44. Quantitative ultrasonometry during pregnancy and lactation: a longitudinal study.
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Hellmeyer L, Hahn B, Fischer C, Hars O, Boekhoff J, Maier J, and Hadji P
- Subjects
- Adult, Female, Humans, Longitudinal Studies, Ultrasonography, Bone Density physiology, Bone Resorption diagnostic imaging, Calcaneus diagnostic imaging, Lactation physiology, Pregnancy physiology
- Abstract
Unlabelled: 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., Introduction: The aim of this study was to evaluate bone changes during pregnancy using the radiation-free method of quantitative ultrasonometry (QUS)., Methods: 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., Results: 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, and >6 months)., Conclusions: 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.
- Published
- 2015
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45. Effect of anastrozole on hormone levels in postmenopausal women with early breast cancer.
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Kyvernitakis I, Albert US, Kalder M, Winarno AS, Hars O, and Hadji P
- Subjects
- Aged, Anastrozole, Bone Density drug effects, Bone Remodeling drug effects, Dehydroepiandrosterone Sulfate blood, Estradiol blood, Female, Follicle Stimulating Hormone blood, Humans, Longitudinal Studies, Luteinizing Hormone blood, Middle Aged, Sex Hormone-Binding Globulin drug effects, Single-Blind Method, Testosterone blood, Antineoplastic Agents, Hormonal pharmacology, Breast Neoplasms blood, Breast Neoplasms drug therapy, Gonadal Steroid Hormones blood, Nitriles pharmacology, Postmenopause blood, Triazoles pharmacology
- Abstract
Objectives: The aim of this study was to investigate the influence of anastrozole on serum hormone levels in postmenopausal women with hormone receptor-positive breast cancer., Methods: We prospectively determined serum levels of estradiol, testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone binding globulin (SHBG), follicle stimulating hormone (FSH) and luteinizing hormone (LH) at screening, as well as after 12 and 24 months of treatment and studied the associations with markers of bone turnover and bone mineral density (BMD)., Results: Altogether, a full set of hormone levels was available for 70 patients. Anastrozole treatment led to decreases of 92.1% for estradiol and 11.1% for LH over the observation period (p < 0.001). Conversely, FSH, DHEAS and testosterone concentrations increased by 5.9%, 33.3% and 50%, respectively (p < 0.001). SHBG levels remained stable during the 24 months of treatment (p = 0.355). There were modest associations between FSH, SHBG, CrossLaps and N-terminal propeptide of human procollagen type I (p < 0.05). Moreover, SHBG correlated positively with the BMD of femoral neck, total hip, total hip T-score, lumbar spine and the lumbar spine T-score, whereas FSH and estradiol correlated with the lumbar spine T-score (p < 0.05)., Conclusions: During the 24 months of follow-up, treatment with anastrozole decreased the serum levels of estradiol and LH. Furthermore, we found notable increases of serum levels of FSH, DHEAS and testosterone in the first 12 months of treatment, stabilizing thereafter. Additionally, we were able to correlate hormone levels with markers of bone turnover and BMD for the first time in this regard.
- Published
- 2015
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46. Persistency with estrogen replacement therapy among hysterectomized women after the Women's Health Initiative study.
- Author
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Kyvernitakis I, Kostev K, Hars O, Albert US, Kalder M, and Hadji P
- Subjects
- Administration, Cutaneous, Administration, Oral, Adult, Age Factors, Female, Gynecology statistics & numerical data, Humans, Hysterectomy, Kaplan-Meier Estimate, Middle Aged, Proportional Hazards Models, Time Factors, Estrogen Replacement Therapy trends, Estrogens administration & dosage, Medication Adherence statistics & numerical data
- Abstract
Objectives: Many women are reluctant to undergo estrogen replacement therapy (ERT) and discontinue the treatment within 12 months. The aim of this study was to investigate the persistence rates of ERT in hysterectomized women over the past decade, reflecting changes in the post-Women's Health Initiative (WHI) era., Methods: We analyzed 8045 patients receiving ERT from 2004 to 2013 using the Disease Analyzer database., Results: After 12 months of follow-up, only 24.6% of patients receiving 1 mg and 24.5% of patients receiving 2 mg of oral ERT were still on treatment (p < 0.0001). The persistency rate of patients receiving <50 μg of transdermal ERT was 28.6% compared to 33.5% for patients receiving >50 μg within the 12 months of follow-up. ERT that began in 2007-2009 was associated with a higher discontinuation rate (hazard ratio 1.06, p = 0.0660) than ERT that began in 2010-2013 (hazard ratio 0.88, p = 0.0001)., Conclusions: Our results indicate low persistency rates in women on ERT irrespective of the dose as well as the route of administration. However, a decrease in discontinuation rates was found when comparing women in the early vs. late post WHI era.
- Published
- 2015
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47. Effect of aromatase inhibition on serum levels of sclerostin and dickkopf-1, bone turnover markers and bone mineral density in women with breast cancer.
- Author
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Kyvernitakis I, Rachner TD, Urbschat A, Hars O, Hofbauer LC, and Hadji P
- Subjects
- Adaptor Proteins, Signal Transducing, Aged, Bone Neoplasms blood, Breast Neoplasms drug therapy, Breast Neoplasms enzymology, Breast Neoplasms pathology, Enzyme-Linked Immunosorbent Assay, Female, Follow-Up Studies, Genetic Markers, Humans, Middle Aged, Osteocytes metabolism, Postmenopause, Prospective Studies, Time Factors, Wnt Proteins antagonists & inhibitors, Antineoplastic Agents pharmacology, Aromatase Inhibitors pharmacology, Biomarkers, Tumor blood, Bone Density drug effects, Bone Morphogenetic Proteins blood, Bone Remodeling drug effects, Breast Neoplasms blood, Intercellular Signaling Peptides and Proteins blood, Osteoprotegerin blood
- Abstract
Purpose: 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., Methods: 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., Results: 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) (p < 0.001) 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., Conclusions: The observed increase in sclerostin levels indicates a central role of osteocytes in bone turnover in women with BC.
- Published
- 2014
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48. Prevalence of menopausal symptoms and their influence on adherence in women with breast cancer.
- Author
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Kyvernitakis I, Ziller V, Hars O, Bauer M, Kalder M, and Hadji P
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- Aged, Anastrozole, Anxiety chemically induced, Chemotherapy, Adjuvant, Female, Hot Flashes chemically induced, Humans, Letrozole, Middle Aged, Musculoskeletal Pain chemically induced, Nitriles adverse effects, Sleep Wake Disorders chemically induced, Time Factors, Triazoles adverse effects, Urinary Bladder Diseases chemically induced, Vaginal Diseases chemically induced, Antineoplastic Agents, Hormonal adverse effects, Aromatase Inhibitors adverse effects, Breast Neoplasms drug therapy, Medication Adherence
- Abstract
Objectives: The use of aromatase inhibitors for the adjuvant treatment of breast cancer may affect the quality of life of patients, as well as adherence to treatment., Methods: Here we report the 2-year results of the 180 patients in the COMPAS study. This is the first randomized, controlled study reporting on menopausal symptoms under endocrine treatment with aromatase inhibitors in breast cancer patients, based on the Menopause Rating Scale. We analyzed the prevalence of menopausal symptoms as well as their associations with patient adherence., Results: Baseline characteristics showed no significant differences among the control and the intervention groups. The majority of women experienced the symptoms at various severities. Overall, we found an increase in the prevalence of hot flushes, sleep disorders, bladder problems, dryness of the vagina as well as of joint and muscular discomfort between the 12- and 24-month visits. In compliant patients, all symptoms except for vaginal dryness improved between the 12- and 24-month visits while, in non-compliant women, hot flushes, irritability, dryness of the vagina as well as joint and muscular discomfort deteriorated. When comparing compliant and non-compliant patients, we found a significant difference only for anxiety (p = 0.028) in the 12-month analysis, as well as a large but non-significant difference for heart discomfort (p = 0.089) in the 24-month visit., Conclusions: Our results indicate that the majority of women treated with aromatase inhibitors are experiencing menopausal symptoms at various severities. We showed that the mean symptom values in compliant patients improve with longer therapy duration. Furthermore, anxiety correlates with better compliance, while heart discomfort may lead to therapy discontinuation.
- Published
- 2014
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49. Impact of BMI on serum estradiol and bone turnover markers in postmenopausal women with hormone-sensitive early breast cancer treated with anastrozole.
- Author
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Kyvernitakis I, Knöll D, Struck M, Hars O, Bauer T, and Hadji P
- Subjects
- Anastrozole, Aromatase Inhibitors therapeutic use, Bone and Bones metabolism, Breast Neoplasms blood, Female, Humans, Middle Aged, Neoplasms, Hormone-Dependent blood, Neoplasms, Hormone-Dependent drug therapy, Neoplasms, Hormone-Dependent metabolism, Obesity blood, Obesity metabolism, Overweight blood, Overweight metabolism, Postmenopause blood, Postmenopause metabolism, Receptors, Estrogen biosynthesis, Body Mass Index, Breast Neoplasms drug therapy, Breast Neoplasms metabolism, Collagen Type I blood, Estradiol blood, Nitriles therapeutic use, Peptide Fragments blood, Peptides blood, Procollagen blood, Triazoles therapeutic use
- Abstract
Purpose: Obesity increases the risk of all-cause and breast cancer mortality. As obese patients have higher levels of aromatase enzyme activity, conflicting results on the effect of body mass index (BMI) of a standard dose aromatase inhibitor on estradiol depletion have been reported., Methods: We prospectively investigated the effect of BMI on the efficacy of anastrozole in 70 postmenopausal women with early, ER-positive breast cancer to decrease serum estradiol assessed by a high-sensitive assay with a sensitivity limit of 5 pg/ml over 24 months. Additionally, we examined the changes of bone markers expecting an inverse relationship., Results: Overall, estradiol decreased from 12.6 pg/ml (SD = 5.4) to 4.0 pg/ml (SD = 5.6) over 24 months (p < 0.001). In contrast, carboxy-terminal collagen crosslinks (CTX) and serum aminoterminal propeptide of type I collagen (PINP) increased from 0.26 ng/ml (SD = 0.18) to 0.40 ng/ml (SD = 0.24) and 41.5 ng/ml (SD = 19.7) to 59.1 ng/ml (SD = 29.1) (p < 0.0001 for both). Baseline estradiol comprised significant differences comparing normal weight with overweight (p < 0.01) or obese patients (p < 0.001). After 12 and 24 months, overweight and obese patients showed a slightly, but insignificantly higher concentrations of estradiol compared to normal weight subjects. We found differences of CTX in comparison between normal weight and obese patients (0.33 vs. 0.21 ng/ml; p < 0.023) at baseline. At 12 and 24 months, there was a significant BMI-independent increase in CTX., Conclusions: Estradiol concentrations in postmenopausal women with early, ER-positive breast cancer on anastrozole were significantly different in normal weight versus overweight or obese patients at baseline, but not at 12 and 24 months. CTX and PINP present a notable increase in the first 12 months of anastrozole treatment, stabilizing thereafter.
- Published
- 2014
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50. Influence of a patient information program on adherence and persistence with an aromatase inhibitor in breast cancer treatment--the COMPAS study.
- Author
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Ziller V, Kyvernitakis I, Knöll D, Storch A, Hars O, and Hadji P
- Subjects
- Aged, Antineoplastic Agents, Hormonal adverse effects, Aromatase Inhibitors adverse effects, Breast Neoplasms pathology, Breast Neoplasms therapy, Combined Modality Therapy, Female, Humans, Middle Aged, Neoplasm Staging, Treatment Outcome, Antineoplastic Agents, Hormonal therapeutic use, Aromatase Inhibitors therapeutic use, Breast Neoplasms drug therapy, Medication Adherence, Patient Education as Topic
- Abstract
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.
- Published
- 2013
- Full Text
- View/download PDF
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