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Osteoporosis: HELP
Articles by Leif Mosekilde
Based on 21 articles published since 2010
(Why 21 articles?)
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Between 2010 and 2020, L. Mosekilde wrote the following 21 articles about Osteoporosis.
 
+ Citations + Abstracts
1 Review Primary hyperparathyroidism: review and recommendations on evaluation, diagnosis, and management. A Canadian and international consensus. 2017

Khan, A A / Hanley, D A / Rizzoli, R / Bollerslev, J / Young, J E M / Rejnmark, L / Thakker, R / D'Amour, P / Paul, T / Van Uum, S / Shrayyef, M Zakaria / Goltzman, D / Kaiser, S / Cusano, N E / Bouillon, R / Mosekilde, L / Kung, A W / Rao, S D / Bhadada, S K / Clarke, B L / Liu, J / Duh, Q / Lewiecki, E Michael / Bandeira, F / Eastell, R / Marcocci, C / Silverberg, S J / Udelsman, R / Davison, K Shawn / Potts, J T / Brandi, M L / Bilezikian, J P. ·McMaster University, Hamilton, Canada. Aliya@mcmaster.ca. · Bone Research and Education Center, 223-3075 Hospital Gate, Oakville, ON, Canada. Aliya@mcmaster.ca. · University of Calgary, Calgary, Canada. · Division of Bone Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland. · University of Oslo, Oslo, Norway. · McMaster University, Hamilton, Canada. · Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark. · University of Oxford, Oxford, UK. · CHUM, Montreal, Canada. · Western University, London, ON, Canada. · Division of Endocrinology, University of Toronto, Mississauga, ON, Canada. · McGill University, Montreal, Canada. · Dalhousie University, Halifax, Canada. · Columbia University College of Physicians and Surgeons, New York, NY, USA. · KU, Leuven, Belgium. · University of Aarhus, Aarhus, Denmark. · University of Hong Kong, Hong Kong, China. · Henry Ford Hospital, Detroit, MI, USA. · Postgraduate Institute of Medical Education and Research, Chandigarth, India. · Mayo Clinic, Rochester, MN, USA. · Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China. · University of California, San Francisco, CA, USA. · New Mexico Clinical Research and Osteoporosis Center, University of New Mexico School of Medicine, Albuquerque, NM, USA. · Division of Endocrinology, Diabetes and Metabolic Bone Diseases, Agamenon Magalhaes Hospital, Brazilian Ministry of Health, University of Pernambuco Medical School, Recife, Brazil. · Department of Human Metabolism, University of Sheffield, Sheffield, UK. · Department for Clinical and Experimental Medicine, University of Pisa, Endocrine Unit 2, University Hospital of Pisa, Pisa, Italy. · Division of Endocrinology, Columbia University College of Physicians and Surgeons, New York, NY, USA. · Department of Surgery, Yale University School of Medicine, New Haven, CT, USA. · University of Victoria, Victoria, BC, Canada. · Massachusetts General Hospital, Harvard University, Boston, MA, USA. · University of Florence, Florence, Italy. ·Osteoporos Int · Pubmed #27613721.

ABSTRACT: The purpose of this review is to assess the most recent evidence in the management of primary hyperparathyroidism (PHPT) and provide updated recommendations for its evaluation, diagnosis and treatment. A Medline search of "Hyperparathyroidism. Primary" was conducted and the literature with the highest levels of evidence were reviewed and used to formulate recommendations. PHPT is a common endocrine disorder usually discovered by routine biochemical screening. PHPT is defined as hypercalcemia with increased or inappropriately normal plasma parathyroid hormone (PTH). It is most commonly seen after the age of 50 years, with women predominating by three to fourfold. In countries with routine multichannel screening, PHPT is identified earlier and may be asymptomatic. Where biochemical testing is not routine, PHPT is more likely to present with skeletal complications, or nephrolithiasis. Parathyroidectomy (PTx) is indicated for those with symptomatic disease. For asymptomatic patients, recent guidelines have recommended criteria for surgery, however PTx can also be considered in those who do not meet criteria, and prefer surgery. Non-surgical therapies are available when surgery is not appropriate. This review presents the current state of the art in the diagnosis and management of PHPT and updates the Canadian Position paper on PHPT. An overview of the impact of PHPT on the skeleton and other target organs is presented with international consensus. Differences in the international presentation of this condition are also summarized.

2 Review Melatonin and the skeleton. 2013

Amstrup, A K / Sikjaer, T / Mosekilde, L / Rejnmark, L. ·Department of Internal Medicine and Endocrinology (MEA), THG Tage-Hansens Gade 2, Aarhus University Hospital, 8000 Aarhus, Denmark, anne_kristine_am@hotmail.com. ·Osteoporos Int · Pubmed #23716040.

ABSTRACT: Melatonin may affect bone metabolism through bone anabolic as well as antiresorptive effects. An age-related decrease in peak melatonin levels at nighttime is well documented, which may increase bone resorption and bone loss in the elderly. In vitro, melatonin reduces oxidative stress on bone cells by acting as an antioxidant. Furthermore, melatonin improves bone formation by promoting differentiation of human mesenchymal stem cell (hMSC) into the osteoblastic cell linage. Bone resorption is reduced by increased synthesis of osteoprogeterin (OPG), a decoy receptor that prevents receptor activator of NK-κB ligand (RANKL) in binding to its receptor. Moreover, melatonin is believed to reduce the synthesis of RANKL preventing further bone resorption. In ovariectomized as well as nonovariectomized rodents, melatonin has shown beneficial effects on bone as assessed by biochemical bone turnover markers, DXA, and μCT scans. Furthermore, in pinealectomized animals, bone mineral density (BMD) is significantly decreased compared to controls, supporting the importance of sufficient melatonin levels. In humans, dysfunction of the melatonin signaling pathway may be involved in idiopathic scoliosis, and the increased fracture risk in nighttime workers may be related to changes in the circadian rhythm of melatonin. In the so-far only randomized study on melatonin treatment, no effects were, however, found on bone turnover markers. In conclusion, melatonin may have beneficial effects on the skeleton, but more studies on humans are warranted in order to find out whether supplementation with melatonin at bedtime may preserve bone mass and improve bone biomechanical competence.

3 Review The pathogenesis, treatment and prevention of osteoporosis in men. 2013

Mosekilde, Leif / Vestergaard, Peter / Rejnmark, Lars. ·Faculty of Health Science, Aarhus University, Denmark. leimos@rm.dk ·Drugs · Pubmed #23329464.

ABSTRACT: Testosterone stimulates longitudinal and appositional growth during childhood, whereas estrogen induces epiphysial closure. During adulthood, testosterone continues to stimulate periosteal growth, whereas estrogen is important for the maintenance of trabecular bone mass and structure. In males, testosterone is aromatized to estradiol. Both free and bioavailable plasma levels of testosterone and estradiol decrease with age in males, and fracture risk is associated with low estradiol levels. Testosterone may increase muscle mass and prevent fractures related to falls. Younger hypogonadal males should be treated with testosterone to attain peak bone mass and increase bone mineral density (BMD). Older hypogonadal males should be treated in cases of osteoporosis, reduced muscle strength and increased risk of falling. Secondary hyperparathyroidism caused by calcium and vitamin D insufficiency may reduce bone mass and strength and increase fracture risk and should be avoided. Since calcium supplementation has been associated with an increased risk of cardiovascular complications and renal stones, the dose should be tailored to the habitual daily calcium intake. Lifestyle-related risk factors (smoking, alcohol consumption, lack of physical activity and low body weight) should be addressed. The antifracture efficacy of antiresorptive and anabolic treatment for osteoporosis has not been documented in larger randomized controlled studies. However, changes in BMD and bone markers suggest similar effects in males and females of bisphosphonates (alendronate, risedronate, ibandronate, zoledronic acid), nasal calcitonin, denosumab and teriparatide (parathyroid hormone [1-34]). The antiresorptive drugs should be used in males with BMD T-score less than -2.5 and one or more risk factors, or with hip and vertebral fractures. It seems appropriate to recommend a higher cut-off T-score (e.g. less than -1.0 standard deviation [SD]) in glucocorticoid-induced osteoporosis and in patients receiving androgen deprivation therapy because of the fast initial bone loss. Anabolic treatment should be used in more severe spinal fracture cases, including glucocorticoid-induced osteoporosis.

4 Review Effects of increasing age, dosage, and duration of PTH treatment on BMD increase--a meta-analysis. 2012

Schwarz, Peter / Jorgensen, Niklas Rye / Mosekilde, Leif / Vestergaard, Peter. ·Department of Medicine, Research Center of Aging and Osteoporosis, Glostrup University Hospital, 2600 Glostrup, Denmark. petsch02@glo.regionh.dk ·Calcif Tissue Int · Pubmed #22237954.

ABSTRACT: We studied the effects of increasing age, dosage, and duration of parathyroid hormone (PTH) treatment on changes in bone mineral density (BMD). Randomized placebo controlled trials on PTH treatment in men or women were retrieved from PubMed (1951 to present), Web of Science (1945 to present), or Embase (1974 to present). The search date was November 16, 2010. All studies comparing PTH treatment to either placebo or antiresorptive drugs--for example, bisphosphonates or hormone replacement therapy--were included. A total of 214 studies were identified in the initial search, and 15 of these trials were included. By metaregression analysis, we found that the increase in spine BMD (Z-score) after PTH treatment was blunted by increasing age (R(2) = 0.27; 2p = 0.01, slope -0.023 Z-scores per year, 11 studies). By increasing PTH dosage (μg/d), spine BMD increased significantly (2p = 0.002) with a slope of +0.011 Z-scores/μg/d of teriparatide. Furthermore, the duration of treatment was positively correlated to spine BMD (P < 0.001) with a slope of +0.043 Z-score for each extra month of treatment. We evaluated the BMD effect in hips and found no age dependency (R(2) = 0.04; P = 0.66; 8 studies). However, for the spine, we found a significant relation to daily dosage (P = 0.011), Z-score coefficient 0.0051 ± 0.0020 (2p < 0.01). The treatment duration also correlated positively by a Z-score coefficient of 0.0170 ± 0.0053, 2p < 0.01 per extra month of treatment. PTH treatment alone seems to be able to improve BMD significantly. However, the BMD increase was significantly lower with increasing age in the spine. No age dependency was observed in the hips. In general the effect of treatment was improved with increasing dosage and duration of treatment from 6 to 36 months.

5 Review Emerging anabolic treatments in osteoporosis. 2011

Mosekilde, Leif / Tørring, Ove / Rejnmark, Lars. ·Department of Internal Medicine and Endocrinology, MEA, Aarhus University Hospital, DK-8000 Aarhus C, Denmark. Leimos@rm.dk ·Curr Drug Saf · Pubmed #21524248.

ABSTRACT: Anabolic treatment that remodels bone tissue and restores bone biomechanical competence is essential in the treatment of osteoporosis. In addition, long term antiresorptive therapy may have limitations because of the reduced renewal of bone tissue. The only pure anabolic drugs available at present are intact PTH (1-84) (Preotact®) and the truncated PTH (1-34) (Teriparatide, Forteo®) while strontium ranelate may possess antiresorptive as well as anabolic properties. The marketed antiresorptive and anabolic antiosteoporotic drugs have limitations in their use due to adverse effects or to the occurrence of rare but severe late complications. Furthermore, indications may be restricted by co-existing diseases or treatment duration may be limited. However, new anabolic drugs are being developed mimicking the effect of PTH, or targeting the calcium sensing receptor (CaSR) or the Wnt/β-catenin signalling pathway. The PTH mimetics are truncated or altered PTH fragments, parathyroid hormone related peptide (PTHrP) and calcilytics stimulating endogenous PTH secretion. Calcimimetics (e.g. strontium) and calcilytics (e.g. lithium) may also affect bone cells directly through the CaSR. The Wnt pathway that stimulates osteoblastic proliferation, differentiation and function may be activated by neutralizing antibodies to secreted inhibitors of Wnt signalling (e.g. Sclerostin or Dickkopf) or by small molecules (e.g. lithium) that inhibits the glycogen synthase kinase 3β mediated degradation of β-catenin. Finally, blocking of activin A by soluble receptor fusion proteins has been shown to increase bone mass by a dual anabolic-antiresorptive action. The present paper summarises the physiological background and the present evidence for these effects.

6 Review New and emerging antiresorptive treatments in osteoporosis. 2011

Rejnmark, Lars / Mosekilde, Leif. ·Department of Endocrinology and Internal Medicine, MEA, Aarhus Sygehus, Aarhus University Hospital, Tage-Hansensgade 2, DK 8000 Aarhus C, Denmark. rejnmark@post6.tele.dk ·Curr Drug Saf · Pubmed #21524247.

ABSTRACT: Bisphosphonates has for many years been the mainstay of antiresorptive treatment, acting predominantly by inducing apoptosis of mature osteoclasts. During recent years, an advanced understanding of the genetic and biological mechanism involved in bone resorption has revealed new therapeutic targets for antiresorptive treatments. Several of these new drugs act by targeting specific pathways within the osteoclastic cells and may reduce bone resorption without a concomitant decrease in bone formation. Such an uncoupling may result in a net bone formation, thereby causing a bone "anabolic" effect through an antiresorptive mechanism. Moreover, in contrast to e.g., bisphosphonates several of the new drugs are not deposited within bone and therefore their duration of action is related to their presence in plasma. Accordingly, their antiresorptive effect is quickly reversible, which may be of advantages if reversal of a suppressed bone turnover is warranted under certain clinical conditions such as osteonecrosis of the jaw. In this paper, we will review the pharmacological properties and clinical effects of drugs that recently have been (denosumab, bazedoxifene, lasofoxifene), or currently are being tested in large phase III clinical trials (Catepsin K inhibitor), as well as drugs that have shown potential beneficial effects in phase I or II trials and may be tested in upcoming phase III trials (integrin antagonists, c-Src kinase inhibitor, inhibitors of the acidification process within the resorption lacuna, and glucagon-like peptide).

7 Article Association between bone indices assessed by DXA, HR-pQCT and QCT scans in post-menopausal women. 2016

Amstrup, Anne Kristine / Jakobsen, Niels Frederik Breum / Moser, Emil / Sikjaer, Tanja / Mosekilde, Leif / Rejnmark, Lars. ·Osteoporosis Clinic, Department of Endocrinology and Internal Medicine (MEA), THG, Aarhus University Hospital, Tage-Hansens Gade 2, Aarhus C, 8000, Aarhus, Denmark. anne_kristine_am@hotmail.com. · Osteoporosis Clinic, Department of Endocrinology and Internal Medicine (MEA), THG, Aarhus University Hospital, Tage-Hansens Gade 2, Aarhus C, 8000, Aarhus, Denmark. ·J Bone Miner Metab · Pubmed #26293682.

ABSTRACT: Quantitative computed tomography (QCT), high-resolution peripheral QCT (HR-pQCT) and dual X-ray absorptiometry (DXA) scans are commonly used when assessing bone mass and structure in patients with osteoporosis. Depending on the imaging technique and measuring site, different information on bone quality is obtained. How well these techniques correlate when assessing central as well as distal skeletal sites has not been carefully assessed to date. One hundred and twenty-five post-menopausal women aged 56-82 (mean 63) years were studied using DXA scans (spine, hip, whole body and forearm), including trabecular bone score (TBS), QCT scans (spine and hip) and HR-pQCT scans (distal radius and tibia). Central site measurements of areal bone mineral density (aBMD) by DXA and volumetric BMD (vBMD) by QCT correlated significantly at the hip (r = 0.74, p < 0.01). Distal site measurements of density at the radius as assessed by DXA and HR-pQCT were also associated (r = 0.74, p < 0.01). Correlations between distal and central site measurements of the hip and of the tibia and radius showed weak to moderate correlation between vBMD by HR-pQCT and QCT (r = -0.27 to 0.54). TBS correlated with QCT at the lumbar spine (r = 0.35) and to trabecular indices of HR-pQCT at the radius and tibia (r = -0.16 to 0.31, p < 0.01). There was moderate to strong agreement between measuring techniques when assessing the same skeletal site. However, when assessing correlations between central and distal sites, the associations were only weak to moderate. Our data suggest that the various techniques measure different characteristics of the bone, and may therefore be used in addition to rather than as a replacment for imaging in clinical practice.

8 Article The effect of melatonin treatment on postural stability, muscle strength, and quality of life and sleep in postmenopausal women: a randomized controlled trial. 2015

Amstrup, Anne Kristine / Sikjaer, Tanja / Mosekilde, Leif / Rejnmark, Lars. ·Department of Endocrinology and Internal Medicine (MEA), Aarhus University Hospital, Tage-Hansens Gade 2 DK-Aarhus C, 8000, Aarhus, Denmark. anne_kristine_am@hotmail.com. · Department of Endocrinology and Internal Medicine (MEA), Aarhus University Hospital, Tage-Hansens Gade 2 DK-Aarhus C, 8000, Aarhus, Denmark. ·Nutr J · Pubmed #26424587.

ABSTRACT: BACKGROUND: Melatonin is often used as a sleeping aid in elderly adults. As previous studies suggest a protective role of melatonin against osteoporosis, it is important to document its safety. Treatment should not cause any hangover effect that could potentially lead to falls and fractures. We therefore aimed to evaluate the effect of melatonin on balance- and muscle function. METHODS AND PATIENTS: In a double-blind placebo-controlled study, we randomized 81 postmenopausal women with osteopenia to receive 1 or 3 mg melatonin, or placebo nightly for 12 months. Postural balance as well as muscle function was measured. In addition, we assessed quality of life and sleep at baseline and after 12 months treatment. RESULTS: Compared to placebo, one-year treatment with melatonin did not affect postural balance or risk of falls. Furthermore, no significant changes between groups were observed in muscle strength in neither upper- nor lower extremities. Treatment did not affect quality of life or sleep. However, in the subgroup of women with sleep disturbances at baseline, a trend towards an improved sleep quality was seen (p = 0.08). CONCLUSION: Treatment with melatonin is safe in postmenopausal women with osteopenia. There is no hangover effect affecting balance- and muscle function following the intake of melatonin. In women with a good quality of sleep, melatonin has no effect, however in poor quality of sleep, small doses of melatonin trended towards improving the quality. TRIAL REGISTRATION: (# NCT01690000).

9 Article Melatonin improves bone mineral density at the femoral neck in postmenopausal women with osteopenia: a randomized controlled trial. 2015

Amstrup, Anne Kristine / Sikjaer, Tanja / Heickendorff, Lene / Mosekilde, Leif / Rejnmark, Lars. ·Department of Endocrinology and Internal Medicine (MEA), Aarhus University Hospital, THG, Aarhus, Denmark. · Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark. ·J Pineal Res · Pubmed #26036434.

ABSTRACT: Melatonin is known for its regulation of circadian rhythm. Recently, studies have shown that melatonin may have a positive effect on the skeleton. By increasing age, the melatonin levels decrease, which may lead to a further imbalanced bone remodeling. We aimed to investigate whether treatment with melatonin could improve bone mass and integrity in humans. In a double-blind RCT, we randomized 81 postmenopausal osteopenic women to 1-yr nightly treatment with melatonin 1 mg (N = 20), 3 mg (N = 20), or placebo (N = 41). At baseline and after 1-yr treatment, we measured bone mineral density (BMD) by dual X-ray absorptiometry, quantitative computed tomography (QCT), and high-resolution peripheral QCT (HR-pQCT) and determined calciotropic hormones and bone markers. Mean age of the study subjects was 63 (range 56-73) yr. Compared to placebo, femoral neck BMD increased by 1.4% in response to melatonin (P < 0.05) in a dose-dependent manner (P < 0.01), as BMD increased by 0.5% in the 1 mg/day group (P = 0.55) and by 2.3% (P < 0.01) in the 3 mg/day group. In the melatonin group, trabecular thickness in tibia increased by 2.2% (P = 0.04), and volumetric bone mineral density (vBMD) in the spine, by 3.6% (P = 0.04) in the 3 mg/day. Treatment did not significantly affect BMD at other sites or levels of bone turnover markers; however, 24-hr urinary calcium was decreased in response to melatonin by 12.2% (P = 0.02). In conclusion, 1-yr treatment with melatonin increased BMD at femoral neck in a dose-dependent manner, while high-dose melatonin increased vBMD in the spine. Further studies are needed to assess the mechanisms of action and whether the positive effect of nighttime melatonin will protect against fractures.

10 Article Vitamin D deficiency in postmenopausal, healthy women predicts increased cardiovascular events: a 16-year follow-up study. 2012

Schierbeck, Louise Lind / Rejnmark, Lars / Tofteng, Charlotte Landbo / Stilgren, Lis / Eiken, Pia / Mosekilde, Leif / Køber, Lars / Jensen, Jens-Erik Beck. ·Department of Endocrinology, Hvidovre Hospital, afd. 541, Kettegård alle 30, 2650 Hvidovre, Denmark. louise.schierbeck@gmail.com ·Eur J Endocrinol · Pubmed #22875588.

ABSTRACT: OBJECTIVE: To investigate the relationship between vitamin D status in healthy women and cardiovascular outcome. DESIGN AND METHODS: Between 1990 and 1993, 2016 healthy, recently postmenopausal women were enrolled in the Danish Osteoporosis Prevention Study. Serum levels of 25-hydroxyvitamin D (25(OH)D, nmol/l) were measured at baseline. Participants were followed for 16 years. The primary end point was a combination of death, heart failure, myocardial infarction (MI) and stroke. Vitamin D deficiency was defined as serum 25(OH)D<50 nmol/l. The primary end point was adjusted for other risk factors of adverse cardiovascular events (age, smoking, blood pressure, hip-waist ratio, education and family history of MI). RESULTS: At baseline, mean age was 50 years and BMI 25. Women with vitamin D deficiency (n=788) had more cardiovascular risk factors than vitamin D-replete women (n=1225). Compared with vitamin D-replete women, women with low 25(OH)D levels had significantly higher BMI and triglycerides, lower HDL and hip-waist ratio and less education. More were smokers among the vitamin D deficient (47 vs 38%). A primary end point was experienced by 118 (15%) with vitamin D deficiency and by 125 (10%) of the vitamin D replete. Hazard ratio (HR) was 1.49 (95% confidence interval: 1.16-1.92; P=0.002) in the vitamin D deficient. Adjusted HR was 1.32 (1.02-1.71; P=0.03). In total, 135 women died; of these, 65 (8%) were of the vitamin D deficient and 70 (6%) in the vitamin D-replete group; unadjusted HR was 1.44 (1.02-2.01; P=0.04) for vitamin D deficiency. CONCLUSION: Healthy women with vitamin D deficiency have increased risk of adverse cardiovascular outcome.

11 Article Oral bisphosphonate use increases the risk for inflammatory jaw disease: a cohort study. 2012

Vestergaard, Peter / Schwartz, Kristoffer / Rejnmark, Lars / Mosekilde, Leif / Pinholt, Else Marie. ·Department of Oral and Maxillofacial Surgery, Institute of Odontology, Faculty of Health Sciences, University of Copenhagen, Denmark. ·J Oral Maxillofac Surg · Pubmed #21764202.

ABSTRACT: PURPOSE: The objective of this study was to address whether among people living in Denmark, those treated with medications to prevent osteoporosis have an increased risk for inflammatory jaw disease compared with those not treated. PATIENTS AND METHODS: A historical cohort study was designed to compare the rate of inflammatory jaw-related events, ie, osteomyelitis, osteitis, periostitis, or sequestrum, between Danish patients who had been prescribed oral bisphosphonates (BP) and other drugs for the treatment of osteoporosis between 1996 and 2006 (the exposed group), and a random sample of the Danish population drawn from a nationwide registry who had not been prescribed oral BPs or other medications to treat osteoporosis (the nonexposed group). The nonexposed subjects were age- and gender-matched to the exposed subjects and randomly drawn from the general population at a ratio of 3 non-BP subjects to 1 BP subject. The primary explanatory variable was oral BP exposure status. Associations between BP treatment and inflammatory jaw events were ascertained using hazard ratios (HR) Cox proportional hazards models. RESULTS: The study sample was composed of 103,562 index subjects and 310,683 control subjects. After adjusting for other factors, including diabetes and chemotherapy, alendronate (HR = 3.15, 95% confidence interval 1.44-6.87) and etidronate (HR = 2.23, 95% confidence interval 1.15-4.31) were associated with an increased risk for inflammatory jaw events. There was no association between oral BP dose and risk for inflammatory jaw events. CONCLUSION: The oral BPs alendronate and etidronate were associated with an increased risk for inflammatory jaw events.

12 Article [Denosumab--a new efficient osteoporosis therapy]. 2011

Rejnmark, Lars / Vestergaard, Peter / Mosekilde, Leif. ·Medicinsk-endokrinologisk Afdeling, Århus Universitetshospital, Århus Sygehus, THG, Aarhus C, Denmark. rejnmark@post6.tele.dk ·Ugeskr Laeger · Pubmed #21276398.

ABSTRACT: Denosumab is a new biological (monoclonal antibody) antiresorptive treatment of osteoporosis which is administrated as a subcutaneous 60 mg injection twice a year. Compared with placebo, three years of treatment increases bone mineral density by 6-9% and decreases the risk of vertebral and hip fractures by 68% and 40%, respectively, in postmenopausal women with osteoporosis. In men with iatrogenic hypogonadism due to prostate cancer, the risk of vertebral fractures is decreased by 62%. Side effects are few, but the treatment may increase risk of infections.

13 Article Use of bisphosphonates and risk of breast cancer. 2011

Vestergaard, Peter / Fischer, Lone / Mele, Marco / Mosekilde, Leif / Christiansen, Peer. ·Department of Endocrinology and Metabolism C, The Osteoporosis Clinic, Aarhus University Hospital, Tage Hansens Gade 2, 8000 Aarhus C, Denmark. p-vest@post4.tele.dk ·Calcif Tissue Int · Pubmed #21253712.

ABSTRACT: A decreased risk of breast cancer has been reported among patients given bisphosphonates. The present aims were to study potential associations between different antiosteoporosis drugs, including bisphosphonates, and the risk of breast cancer before and after start of treatment and to appraise possible dose-effect relationships. From national Danish registers, all female users of bisphosphonates aged ≥40 years and other drugs against osteoporosis between 1996 and 2006 were identified (n = 87,104). This cohort was compared with a control group, where each patient was matched on age with three nonexposed women from the general population (n = 261,322). Before start of most drugs against osteoporosis an increased risk of breast cancer was seen compared to controls (e.g., adjusted OR = 1.09, 95% CI 1.04-1.16 for alendronate). This excess risk was higher in younger women (e.g., OR = 4.48, 95% CI 2.98-6.75 for alendronate in women ≤50 years) and disappeared in women older than 70 years (e.g., OR = 0.95, 95% CI 0.88-1.01 for alendronate). In contrast, a decreased risk of breast cancer was seen after start of alendronate (HR = 0.53, 95% CI 0.38-0.73), etidronate (HR = 0.80, 95% CI 0.73-0.89), and raloxifene (HR = 0.53, 95% CI 0.38-0.73). No dose-response relationship was present for alendronate and etidronate, whereas a decreasing risk was seen with increasing daily dose of raloxifene. Bisphosphonate treatment in women was associated with a reduced risk of breast cancer. However, no causal relationship seemed to be present.

14 Article Risk of femoral shaft and subtrochanteric fractures among users of bisphosphonates and raloxifene. 2011

Vestergaard, P / Schwartz, F / Rejnmark, L / Mosekilde, L. ·Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark. p-vest@post4.tele.dk ·Osteoporos Int · Pubmed #21165600.

ABSTRACT: INTRODUCTION: The objective of this study is to determine the association between drugs against osteoporosis and the risk of femoral shaft and subtrochanteric fractures. No separation was made between atypical and typical fractures. METHODS: Nationwide cohort study from Denmark with all users of bisphosphonates and other drugs against osteoporosis between 1996 and 2006 (n = 103,562) as exposed group and three age- and gender-matched controls from the general population (n = 310,683). Adjustments were made for prior fracture, use of systemic hormone therapy, and use of systemic corticosteroids. RESULTS: After initiation of therapy, an increased risk of subtrochanteric fractures was seen for alendronate (hazard ratio (HR) = 2.41, 95% confidence interval (CI) 1.78-3.27), etidronate (HR = 1.96, 95% CI 1.62-2.36), and clodronate (HR = 20.0, 95% CI 1.94-205), but not for raloxifene (HR = 1.06, 95% CI 0.34-3.32). However, an increased risk of subtrochanteric fractures was also present before the start of alendronate (OR = 2.36, 95% CI 2.05-2.72), etidronate (OR = 3.05, 95% CI 2.59-3.58), clodronate (OR = 10.8, 95% CI 1.14-103), raloxifene (OR = 1.90, 95% CI 1.07-3.40), and strontium ranelate (OR = 2.97, 95% CI 1.07-8.27). Similar trends were seen for femoral shaft fractures and overall fracture risk. After the start of etidronate, no dose-response relationship was present (p for trend, 0.54). For alendronate, a decreasing risk was present with increasing average daily dose (p for trend, <0.01). CONCLUSIONS: Although an increased risk of femoral shaft and subtrochanteric fractures are seen with the use of several types of bisphosphonates, the increased risk before the start of the drugs may point at an effect of the underlying disease being treated. The increased risk may, thus, perhaps be due to confounding by indication.

15 Article Are antiresorptive drugs effective against fractures in patients with diabetes? 2011

Vestergaard, Peter / Rejnmark, Lars / Mosekilde, Leif. ·The Osteoporosis Clinic, Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Denmark. p-vest@post4.tele.dk ·Calcif Tissue Int · Pubmed #21161194.

ABSTRACT: We studied whether the reduction in bone turnover by use of antiresorptive drugs is detrimental in patients with diabetes who already have low bone turnover due to hyperglycemia in a nationwide cohort study from Denmark. All users of antiresorptive drugs against osteoporosis between 1996 and 2006 (n = 103,562) were the exposed group, with three age- and gender-matched controls from the general population (n = 310,683). Patients on bisphosphonates and raloxifene had a higher risk of hip, spine, and forearm fractures. However, no difference was observed in the antifracture efficacy between patients with diabetes and nondiabetic controls or between patients with type 1 and type 2 diabetes. Too few were users of strontium to allow analysis for this compound. The excess risk of fractures among patients treated with bisphosphonates or raloxifene compared to nonexposed controls was due to the higher a priori risk of fractures among patients treated for osteoporosis. Diabetes does not seem to affect the fracture-preventive potential of bisphosphonates or raloxifene. The low-turnover state of diabetes thus does not seem to be a hindrance to the effect of these drugs against osteoporosis. Therefore, patients with diabetes should receive treatment for osteoporosis in the same way as nondiabetic patients.

16 Article Polymorphisms in the ALOX12 gene and osteoporosis. 2011

Harsløf, T / Husted, L B / Nyegaard, M / Carstens, M / Stenkjær, L / Brixen, K / Eiken, P / Jensen, J-E B / Børglum, A D / Mosekilde, L / Rejnmark, L / Langdahl, B L. ·Department of Endocrinology and Internal Medicine, THG, Aarhus University Hospital, 8000, Aarhus C, Denmark. torbhars@rm.dk ·Osteoporos Int · Pubmed #21104233.

ABSTRACT: INTRODUCTION: Stimulation of the PPARγ with ligands produced by the ALOX enzymes drives mesenchymal stem cells in an adipocyte direction at the expense of osteoblasts leading to decreased osteoblast number and BMD. Previously, polymorphisms in the ALOX12 gene have been associated with osteoporosis. METHODS: We examined the effect of ALOX12 polymorphisms on BMD and the risk of fractures in two Danish cohorts: AROS, a case-control population comprising 809 individuals and DOPS, a population comprising 1,716 perimenopausal women allocated to hormone therapy or not at baseline and followed for up to 10 years. On the basis of linkage disequilibrium (LD) between SNPs throughout the gene and previous genetic association studies we chose ten polymorphisms for investigation. Genotyping was carried out using the Sequenom MassARRAY genotyping system and TaqMan assays. RESULTS: In AROS, individuals heterozygous for the polymorphisms rs3840880, rs9897850, rs2292350 and rs1126667 had a 3.0-4.7% decreased lumbar spine BMD (p = 0.02-0.06) and an increased risk of vertebral fractures (p < 0.05) compared with individuals homozygous for either allele. In DOPS, none of the individual SNPs were associated with BMD or incident fractures. In both cohorts, the above-mentioned SNPs comprised an LD-block (pairwise D´ = 1.0, r (2) = 0.45-0.97). A haplotype comprising all the common alleles (frequency 9%) was associated with decreased bone loss at the hip (p < 0.05) and decreased incidence of osteoporotic fractures (p < 0.05) in DOPS and increased femoral neck BMD in AROS (p < 0.05). CONCLUSION: Our study suggests that genetic variants in ALOX12 may influence BMD and fracture risk.

17 Article Polymorphisms of the peroxisome proliferator-activated receptor γ (PPARγ) gene are associated with osteoporosis. 2011

Harsløf, T / Tofteng, C L / Husted, L B / Nyegaard, M / Børglum, A / Carstens, M / Stenkjær, L / Brixen, K / Eiken, P / Jensen, J-E B / Mosekilde, L / Rejnmark, L / Langdahl, B L. ·Department of Endocrinology and Internal Medicine THG, Aarhus University Hospital, 8000, Århus C, Denmark. torbhars@rm.dk ·Osteoporos Int · Pubmed #21104228.

ABSTRACT: INTRODUCTION: Stimulation of PPARγ causes development of mesenchymal stem cells to adipocytes instead of osteoblasts leading to decreased osteoblast number and BMD. The aim of this study was to examine the effect of PPARG polymorphisms on BMD and fracture risk in two Danish cohorts: AROS, a case-control population comprising 809 individuals and DOPS, a population comprising 1,716 perimenopausal women allocated to hormone therapy or not at baseline and followed for 10 years. On the basis of linkage disequilibrium between SNPs throughout the gene and previous studies we chose 10 polymorphisms for investigation. METHODS: In AROS, individuals heterozygous for the polymorphisms rs12497191, rs4135263, and rs1151999 had an increased risk of vertebral fractures (OR = 1.48-1.76, p = 0.005-0.04) compared with individuals homozygous for the common allele. In DOPS, individuals heterozygous for rs1151999 had an increased BMD at the hip sites (p ≤ 0.02). An interaction between rs1151999 and diet was found on BMD in both cohorts. RESULTS: For the polymorphism rs1152003 there was an interaction with body weight on BMD at all sites in both cohorts (p ≤ 0.07). Stratified analyses revealed that in the high weight group in AROS individuals homozygous for the variant allele had a decreased BMD (p ≤ 0.02), whereas the same pattern was found in the low weight group in DOPS (p ≤ 0.03). A number of haplotype associations were found as well, the direction of which was opposite in the two cohorts. CONCLUSION: Our study suggests an association SNPs in PPARG and haplotypes thereof and BMD and fracture risk. The effect however appears to be modifiable by environmental factors.

18 Article Bone mineral density in Klinefelter syndrome is reduced and primarily determined by muscle strength and resorptive markers, but not directly by testosterone. 2011

Bojesen, A / Birkebæk, N / Kristensen, K / Heickendorff, L / Mosekilde, L / Christiansen, J S / Gravholt, C H. ·Department of Clinical Genetics, Vejle Hospital, DK-7100 Vejle, Denmark. ·Osteoporos Int · Pubmed #20658127.

ABSTRACT: SUMMARY: Klinefelter syndrome (KS) patients have lower bone mineral density (BMD) at the spine, hip and forearm compared to healthy subjects, but frank osteoporosis is not common. Muscle strength and bone markers predicted BMD but KS itself and serum testosterone did not. Low vitamin D and high PTH were frequent among KS. INTRODUCTION: The long-term consequence of KS on bone health is not well described. The objective of this study is to investigate the regional BMD and its determinants in KS. METHODS: This is a cross-sectional study. BMD at the spine, hip and forearm are measured by DXA and correlated to biochemical markers of bone turnover, vitamin D metabolites, PTH, sex hormones, growth factors as well as muscle strength and anthropometric measures. The setting is at a university clinical research centre. The study involves 70 adult KS patients and 71 age-matched healthy subjects. RESULTS: In KS, BMD was universally lowered in all regions. Markers of bone formation or bone resorption were not altered in KS, but 25-OH-Dvitamin was lower (55 vs. 82 nmol/L, p < 0.0001) than in healthy subjects. Significantly more KS patients had low BMD (Z-scores below -2) at the forearm (15 KS vs. two healthy subjects, p = 0.001) but not at the spine or hip. Muscle strength (bicep and quadriceps) was lower among KS patients. Multivariate analysis revealed that muscle strength, treatment with testosterone (ever/never), age at diagnosis, SHBG, bone-specific alkaline phosphatase and 1CTP were all independent predictors of BMD, but androgens was not. CONCLUSIONS: KS patients had lower BMD at the spine, hip and forearm compared to age-matched healthy subjects, but frank osteoporosis was not common. Muscle strength, previous history of testosterone treatment, age at diagnosis and bone markers were predictors of BMD, but testosterone was not. Signs of secondary hyperparathyroidism were present among KS. Dietary intake of vitamin D or sun exposure may be lower in KS patients.

19 Article Stroke in relation to use of raloxifene and other drugs against osteoporosis. 2011

Vestergaard, P / Schwartz, K / Pinholt, E M / Rejnmark, L / Mosekilde, L. ·Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Tage Hansens Gade 2, DK-8000 Arhus C, Denmark. p-vest@post4.tele.dk ·Osteoporos Int · Pubmed #20449570.

ABSTRACT: PURPOSE: We aim to study the association between use of raloxifene and other drugs against osteoporosis and risk of stroke. METHODS: This is a nationwide cohort study from Denmark. All users of bisphosphonates and other drugs against osteoporosis between 1996 and 2006 (n = 103,562) as exposed group and three age- and gender-matched controls from the general population (n = 310,683). RESULTS: Before the drugs were started, patients later initiating alendronate or raloxifene had fewer strokes than the controls. In contrast, patients who later did start clodronate have more strokes. Among the later users of other bisphosphonates, strontium ranelate or parathyroid hormone, no change in the risk of stroke was present. Patients who started raloxifene neither had an excess risk of strokes nor of fatal strokes. No dose-response relationship was present. Among users of alendronate, a decreasing overall risk of stroke was seen with increasing dose. However, for fatal strokes, the risk increased with increasing dose of alendronate. Among users of etidronate, no trend with dose was present for overall stroke risk; whereas for fatal strokes, an increasing risk was seen with increasing dose of etidronate. CONCLUSIONS: Raloxifene does not seem associated with an excess risk of strokes. The increase seen for alendronate did not seem to be causal as no classical dose-response relationship was present. The dose-response relationship for fatal strokes with alendronate and etidronate needs further examination. However, the excess risks were small and may be due to the underlying disease.

20 Article Effects of smoking on severity of disease in primary hyperparathyroidism. 2010

Amstrup, Anne Kristine / Rejnmark, Lars / Vestergaard, Peter / Heickendorff, Lene / Mosekilde, Leif. ·Department of Endocrinology and Metabolism (MEA), Aarhus Sygehus, Aarhus University Hospital, Tage-Hansens Gade 2, 8000, Aarhus C, Denmark. anne_kristine_am@hotmail.com ·Calcif Tissue Int · Pubmed #20862465.

ABSTRACT: In healthy subjects, smoking is associated with lower plasma levels of parathyroid hormone (PTH) and decreased bone mineral density (BMD). The effect of smoking on PTH, skeletal metabolism, and size/histology of the parathyroid glands in primary hyperparathyroidism (PHPT) is unknown. We investigated, in a cross-sectional study, whether smoking affects PTH levels, BMD, and weight/histology of removed parathyroid tissue in PHPT. We studied 344 (285 women) parathyroidectomized patients with PHPT (24% smokers). Biochemistry was determined at the time of diagnosis. BMD was measured before and after surgical cure. Smoking was associated with lower PTH (9.9 ± 1.8 [SD] vs. 12.2 ± 1.8 pmol/l, P < 0.01) and higher phosphate (0.95 ± 0.17 vs. 0.86 ± 0.17 mmol/l, P < 0.01) levels. Adjustments for between-group differences in age, sex, body weight, plasma creatinine, and 25-hydroxyvitamin D (25OHD) levels did not change the findings. Neither weight of removed adenomatous and hyperplastic tissue nor BMD differed according to smoking status. After adjustment for body weight, age, sex, and 25OHD levels, smokers had slightly lower BMD at the whole body but not at the spine, hip, or forearm. Independent of smoking status, surgical cure caused a significant increase in BMD at all measurement sites. In PHPT smoking is associated with lower plasma PTH and higher phosphate levels. Adjustment for confounders of PTH did not change the results. In contrast to healthy subjects, smoking seems not to decrease BMD in PHPT. Smoking may compromise the correct diagnostic evaluation of borderline hyperparathyroidism. It is unknown to what extent smoking in PHPT affects fracture risk and indication for surgery.

21 Article Risk of atrial fibrillation associated with use of bisphosphonates and other drugs against osteoporosis: a cohort study. 2010

Vestergaard, Peter / Schwartz, Kristoffer / Pinholt, Else Marie / Rejnmark, Lars / Mosekilde, Leif. ·Department of Endocrinology and Metabolism C, Aarhus University Hospital, Tage Hansens Gade 2, 8000 Arhus C, Denmark. p-vest@post4.tele.dk ·Calcif Tissue Int · Pubmed #20309678.

ABSTRACT: We studied the association between bisphosphonate use and risk of atrial fibrillation or flutter and the effect of confounders such as heart and lung disease in a nationwide retrospective cohort from Denmark. All users of bisphosphonates and other drugs against osteoporosis between 1996 and 2006 (n = 103,562) were the exposed group and three age- and gender-matched controls from the general population (n = 310,683) were the nonexposed group. The main outcome measure was atrial fibrillation or atrial flutter. Before initiation of treatment against osteoporosis, no excess of atrial fibrillation or flutter was present for any drug except for etidronate (OR = 1.22, 95% CI 1.15-1.29). After initiation of treatment, raloxifene was not associated with any excess risk of atrial fibrillation (OR = 0.98, 95% CI 0.72-1.33). Etidronate (HR = 1.08, 95% CI 1.02-1.14) and alendronate (HR = 1.09, 95% CI 1.00-1.20) were associated with an excess risk of atrial fibrillation after treatment start if statistical adjustments were made for cardiovascular disease. However, this association disappeared upon statistical adjustment for chronic obstructive pulmonary disease (COPD) (etidronate HR = 1.04, 95% CI 0.98-1.10; alendronate HR = 1.05, 95% CI 0.96-1.15). In patients using etidronate (12.5% vs. 3.8%) and alendronate (11.4% vs. 4.6%) major differences were present in prevalence of COPD at start of treatment compared to matched controls. In conclusion, oral bisphosphonates do not seem to be associated with an excess risk of atrial fibrillation. Any excess risk seen in prior studies may be due to confounding from COPD.