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Live Fluorescent Staining Platform for Drug-Screening and Mechanism-Analysis in Zebrafish for Bone Mineralization. Molecules 2017; 22:molecules22122068. [PMID: 29186901 PMCID: PMC6149919 DOI: 10.3390/molecules22122068] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2017] [Revised: 11/10/2017] [Accepted: 11/22/2017] [Indexed: 11/21/2022] Open
Abstract
Currently, drug screening relies on cell-based experiments or on animal models to confirm biological effects. The mammalian system is considered too time-consuming, expensive and complex to perform high-throughput drug screening. There is a gap between in vitro cell-based models and the in vivo mammalian models. The zebrafish is an ideal model that could link preclinical toxicity screening with the drug development pipeline. Taking advantage of a highly conservative genomic, rapid development, large number of offspring, low cost and easy manipulation, zebrafish has been considered an excellent animal model for disease-based drug screening. In this study, zebrafish embryos were incubated with small molecular compounds that potentially affected bone mineralization in microplates. Two compounds of alendronate and dorsomorphin were used as positive and negative controls, respectively. The level of osteogenic mineralization was measured and quantified by using ImageJ software with fluorescent calcein-staining images. Among twenty-four tested compounds from the kinase inhibitor library, we identified two compounds, pentamidine and BML-267, which showed increased embryonic mineralization; while six compounds, RWJ-60475, levamisole HCL, tetramisole HCL, fenvalerate, NSC-663284, and BML-267ester, were inhibitory to bone mineralization. In addition, real time quantitative PCR (RT-qPCR) was performed to evaluate the biological pathways involved in bone metabolism at the molecular level. We confirmed that alendronate enhanced the level of bone mineralization by inhibiting osteoclast-related genes. In summary, our research established a simple method to screen potential bone metabolic drugs and to perform mechanism analysis for bone mineralization in vivo.
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Effective treatment of delayed union of a lumbar vertebral fracture with daily administration of teriparatide in a patient with diffuse idiopathic skeletal hyperostosis. EUROPEAN SPINE JOURNAL : OFFICIAL PUBLICATION OF THE EUROPEAN SPINE SOCIETY, THE EUROPEAN SPINAL DEFORMITY SOCIETY, AND THE EUROPEAN SECTION OF THE CERVICAL SPINE RESEARCH SOCIETY 2015; 24 Suppl 4:S573-6. [PMID: 25649182 DOI: 10.1007/s00586-014-3733-9] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/24/2014] [Revised: 12/21/2014] [Accepted: 12/21/2014] [Indexed: 10/24/2022]
Abstract
INTRODUCTION We herein describe a case of delayed union of a lumbar spine fracture in a 70-year-old patient with diffuse idiopathic skeletal hyperostosis (DISH). CLINICAL COURSE AND RESULT Because he decided not to undergo surgical treatment, we provided conservative treatment with teriparatide (TPTD). Union was obtained in 2 months, and no adverse events were observed during treatment. Six months after starting the TPTD, further bone formation was observed and the lumbar instability had resolved. CONCLUSION This is the first report of successful use of TPTD to treat delayed union of a spine fracture in a patient with DISH without surgical intervention.
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Kang D, Liu Z, Wang Y, Zhang H, Feng X, Cao W, Wang P. Relationship of body composition with bone mineral density in northern Chinese men by body mass index levels. J Endocrinol Invest 2014; 37:359-67. [PMID: 24477947 DOI: 10.1007/s40618-013-0037-6] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2012] [Accepted: 12/01/2013] [Indexed: 10/25/2022]
Abstract
UNLABELLED Osteoporosis and obesity are severe public health problems in an aging society, and as we all know, bone mineral density (BMD) is closely related to fat mass (FM) and fat distribution. However, studies have long focused on pre- or post-menopausal women, and its presence in men has been underestimated. To investigate the differential impact of fat on BMD, we characterized body composition of northern Chinese men and examined the relationship with BMD according to body mass index (BMI) levels. METHODS A cross-sectional study was conducted on 502 healthy northern Chinese men aged 20-89 screened from the participants in a community-based osteoporosis prevention study conducted by the Research Center of Qianfoshan Hospital of Shandong University from 2009 to 2010. The qualified subjects were stratified according to BMI levels as normal weight (18.5 ≤ BMI < 24 kg/m(2), n = 137), overweight (24 ≤ BMI < 28 kg/m(2), n = 225), and obesity (BMI ≥ 28 kg/m(2), n = 140). Total body, left femur, lumbar spine BMD and lean mass (LM), FM, percent body fat (%BF) were measured by dual-energy X-ray absorptiometry. Pearson correlation and age-adjusted partial correlation analyses between body composition-related parameters and BMD were performed. Multiple regression analysis was performed to examine the relationship of BMD with LM, FM and %BF. RESULTS Height and weight had positive associations with BMD at all sites, although age had negative associations. Of all subjects, LM and FM were positively correlated with BMD at almost sites (P < 0.01). However, when the subjects were divided into normal weight, overweight and obesity, no relations were reflected between FM and BMD. %BF showed negative correlations with BMD at arm and leg (P < 0.01) in overweight, and with BMD at total body, arm, leg, hip (P < 0.01) in obesity. In regression models, both FM and LM showed statistically positively significant relations with total body and regional BMD in all subjects (all P < 0.05). LM was positively correlated with BMD at almost site (all P < 0.05) in groups, while FM had no association. Interestingly, percent body fat (%BF) had negative associations with BMD at total body, arm, leg and total femur in overweight and obesity. CONCLUSIONS The relationship between LM and BMD was certain in northern Chinese men while fat-bone relationship was complicated. %BF had a significantly negative association with total body and regional BMD in overweight and obese men.
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Affiliation(s)
- D Kang
- Department of Endocrinology, Qianfoshan Hospital of Shandong University, No. 16766 Jingshi Road, Jinan, 250014, China,
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Lotan M, Reves-Siesel R, Eliav-Shalev RS, Merrick J. Osteoporosis in Rett syndrome: a case study presenting a novel management intervention for severe osteoporosis. Osteoporos Int 2013; 24:3059-63. [PMID: 23828127 DOI: 10.1007/s00198-013-2423-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2013] [Accepted: 05/31/2013] [Indexed: 10/26/2022]
Abstract
The present article describes a successful novel therapeutic intervention with Aredia with one child with Rett syndrome, after suffering from six pathological fractures within less than 3 years due to severe osteoporosis. Since the initiation of the treatment (3 years ago), the child has not suffered any fractures. Patients with chronic diseases and those with disabilities or on anticonvulsant medications are at risk for low bone density and possibly for the resultant pathologic fractures that define osteoporosis in children. Individuals with Rett syndrome (RS) have been shown to have low bone mineral density (or osteopenia) at a young age. If osteoporosis occurs in a girl with RS, it can inflict pain and seriously impair the child's mobility and quality of life. The present article describes a case study of a child with RS (showing an average of 1.75 fractures annually for the 4 years preceding the treatment) before and after a treatment with Aredia. Patient received 30 mg/day for 3 days on a once every 3-month cycle. There was a 45 % improvement in bone mass density (BMD) values from pre-post-intervention. The child had no fractures in the 3 years posttreatment. This finding is significant (p < 0.03). The BMD Z-scores of the child showed severe osteoporosis (Z-score of -3.8) at pre-intervention and are elevated to osteopenia levels (Z-score of -1.3) at post-intervention measurements. All measurements suggest that the treatment successfully reversed the osteoporotic process and prevented further fractures. This change caused great relief to the child and her family and an improvement in their quality of life. The findings support the ability (in one case) to reverse the progression of osteoporosis in individuals with Rett syndrome showing severe osteoporosis with multiple fractures.
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Affiliation(s)
- M Lotan
- Israeli Rett Center, National Rett Syndrome Evaluation Team, Chaim Sheba Medical Center, Tel HaShomer, Ramat Gan, Israel,
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Nur H, Toraman NF, Arica Z, Sarier N, Samur A. The relationship between body composition and bone mineral density in postmenopausal Turkish women. Rheumatol Int 2012; 33:607-12. [PMID: 22481215 DOI: 10.1007/s00296-012-2391-7] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2011] [Accepted: 03/11/2012] [Indexed: 10/28/2022]
Abstract
In a retrospective cross-sectional study among 202 postmenopausal women aged 46-75 years, we aimed to investigate the relationship between body composition and bone mineral density (BMD) to determine whether fat mass or lean mass is a better determinant of BMD in Turkish postmenopausal women. Lumbar spine (L1-L4) and proximal femur BMD were measured by dual energy X-ray absorbsiometry. Body composition analysis was performed by bioelectric impedance method and fat mass, lean mass, and percent fat were measured. Both fat mass and lean mass were positively correlated with BMD at the lumbar spine and proximal femur, weight and body mass index. Lean mass was also positively correlated with height and negatively correlated with age and years since menopause (P < 0.01). The correlations of fat mass and lean mass with BMD at the lumbar spine and proximal femur remained significant after adjustment for age, years since menopause and height. When the lean mass was adjusted together with age, years since menopause and height, the significant relationship between the fat mass and BMD continued, however the significant correlation between the lean mass and BMD disappeared at all sites after adjustment for fat mass. In multiple regression analyses, fat mass was the significant determinant of all BMD sites. Our data suggest that fat mass is the significant determinant of BMD at the lumbar spine and proximal femur, and lean mass does not have an impact on BMD when fat mass was taken into account in Turkish postmenopausal women.
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Affiliation(s)
- Hakan Nur
- Department of Physical Medicine and Rehabilitation, Antalya Education and Research Hospital, Antalya, Turkey.
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Jaglal SB, Donescu OS, Bansod V, Laprade J, Thorpe K, Hawker G, Majumdar SR, Meadows L, Cadarette SM, Papaioannou A, Kloseck M, Beaton D, Bogoch E, Zwarenstein M. Impact of a centralized osteoporosis coordinator on post-fracture osteoporosis management: a cluster randomized trial. Osteoporos Int 2012; 23:87-95. [PMID: 21779817 PMCID: PMC3249212 DOI: 10.1007/s00198-011-1726-7] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2011] [Accepted: 06/01/2011] [Indexed: 11/30/2022]
Abstract
UNLABELLED We conducted a cluster randomized trial evaluating the effect of a centralized coordinator who identifies and follows up with fracture patients and their primary care physicians about osteoporosis. Compared with controls, intervention patients were five times more likely to receive BMD testing and two times more likely to receive appropriate management. INTRODUCTION To determine if a centralized coordinator who follows up with fracture patients and their primary care physicians by telephone and mail (intervention) will increase the proportion of patients who receive appropriate post-fracture osteoporosis management, compared to simple fall prevention advice (attention control). METHODS A cluster randomized controlled trial was conducted in small community hospitals in the province of Ontario, Canada. Hospitals that treated between 60 and 340 fracture patients per year were eligible. Patients 40 years and older presenting with a low trauma fracture were identified from Emergency Department records and enrolled in the trial. The primary outcome was 'appropriate' management, defined as a normal bone mineral density (BMD) test or taking osteoporosis medications. RESULTS Thirty-six hospitals were randomized to either intervention or control and 130 intervention and 137 control subjects completed the study. The mean age of participants was 65 ± 12 years and 69% were female. The intervention increased the proportion of patients who received appropriate management within 6 months of fracture; 45% in the intervention group compared with 26% in the control group (absolute difference of 19%; adjusted OR, 2.3; 95% CI, 1.3-4.1). The proportion who had a BMD test scheduled or performed was much higher with 57% of intervention patients compared with 21% of controls (absolute difference of 36%; adjusted OR, 4.8; 95% CI, 3.0-7.0). CONCLUSIONS A centralized osteoporosis coordinator is effective in improving the quality of osteoporosis care in smaller communities that do not have on-site coordinators or direct access to osteoporosis specialists.
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Affiliation(s)
- S B Jaglal
- Toronto Rehabilitation Institute, Toronto, ON, Canada.
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Datta NS. Osteoporotic fracture and parathyroid hormone. World J Orthop 2011; 2:67-74. [PMID: 22474638 PMCID: PMC3302045 DOI: 10.5312/wjo.v2.i8.67] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2011] [Revised: 04/19/2011] [Accepted: 06/01/2011] [Indexed: 02/06/2023] Open
Abstract
Osteoporosis and age-related bone loss is associated with changes in bone remodeling characterized by decreased bone formation relative to bone resorption, resulting in bone fragility and increased risk of fractures. Stimulating the function of bone-forming osteoblasts, is the preferred pharmacological intervention for osteoporosis. Recombinant parathyroid hormone (PTH), PTH(1-34), is an anabolic agent with proven benefits to bone strength and has been characterized as a potential therapy for skeletal repair. In spite of PTH's clinical use, safety is a major consideration for long-term treatment. Studies have demonstrated that intermittent PTH treatment enhances and accelerates the skeletal repair process via a number of mechanisms. Recent research into the molecular mechanism of PTH action on bone tissue has led to the development of PTH analogs to control osteoporotic fractures. This review summarizes a number of advances made in the field of PTH and bone fracture to combat these injuries in humans and in animal models. The ultimate goal of providing an alternative to PTH, currently the sole anabolic therapy in clinical use, to promote bone formation and improve bone strength in the aging population is yet to be achieved.
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Genaro PS, Pereira GA, Pinheiro MM, Szejnfeld VL, Martini LA. Influence of body composition on bone mass in postmenopausal osteoporotic women. Arch Gerontol Geriatr 2010; 51:295-8. [DOI: 10.1016/j.archger.2009.12.006] [Citation(s) in RCA: 66] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2009] [Revised: 12/12/2009] [Accepted: 12/19/2009] [Indexed: 11/30/2022]
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Cesareo R, Napolitano C, Iozzino M. Strontium ranelate in postmenopausal osteoporosis treatment: a critical appraisal. Int J Womens Health 2010; 2:1-6. [PMID: 21072291 PMCID: PMC2971725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2009] [Indexed: 11/02/2022] Open
Abstract
Osteoporosis is a progressive and debilitating disease characterized by a massive bone loss with a deterioration of bone tissues, and a propensity for a fragility fracture. Strontium ranelate is the first antiosteoporotic treatment that has dual mode of action and simultaneously increases bone formation, while decreasing bone resorption, thus rebalancing bone turnover formation. Strontium ranelate rebalances bone turnover in favor of improved bone geometry, cortical thickness, trabecular bone morphology and intrinsic bone tissue quality, which translates into enhanced bone strength. This review describes the mechanism of the strontium ranelate action and its effects on bone mineral density, bone turnover, and osteoporotic fractures. The efficacy of strontium ranelate in postmenopausal osteoporosis treatment to reduce the risk of vertebral and hip fractures has been highlighted in several randomized, controlled trials. Treatment efficacy with strontium ranelate has been documented across a wide range of patient profiles: age, number of prevalent vertebral fractures, body mass index, and a family history of osteoporosis. Because strontium ranelate has a large spectrum of efficacy, it can be used to treat different subgroups of patients with postmenopausal osteoporosis. Strontium ranelate was shown to be relatively well tolerated and the safety aspects were good. Strontium ranelate should be considered as a first-line treatment for postmenopausal osteoporotic patients.
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Affiliation(s)
- Roberto Cesareo
- Department of Internal Medicine,,Correspondence: Roberto Cesareo, Department of Internal Medicine, S.M. Goretti Hospital, Italy, Tel +39 0773 6553751, Fax +39 0773 6553751, Email
| | | | - Mario Iozzino
- Department of Radiology, S.M. Goretti Hospital, Latina, Italy
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Teriparatide may accelerate healing in delayed unions of type III odontoid fractures: a report of 3 cases. ACTA ACUST UNITED AC 2010; 23:151-5. [PMID: 20051918 DOI: 10.1097/bsd.0b013e31819a8b7a] [Citation(s) in RCA: 90] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
STUDY DESIGN Case Report. OBJECTIVE To report on the treatment of 3 cases of painful delayed unions of type III odontoid fractures with teriparatide. SUMMARY OF BACKGROUND DATA Fractures of the C2 vertebra, also known as odontoid fractures, are an important subset of cervical spine fractures. Type III odontoid fractures pass through predominately cancellous bone of C2. Generally accepted treatment is external immobilization with either a rigid collar or a halo vest for 8 to 12 weeks. We report 3 patients who, despite external immobilization, developed painful delayed unions of type III odontoid fractures. Teriparatide is a novel anabolic drug therapy for osteoporosis. It has been shown to stimulate osteoblasts, enhance bone connectivity, increase endosteal cortical thickness, and improve bone mineral content. The drug is given through subcutaneous injection of 20 microg/d for between 6 weeks and 2 years. We treated these 3 patients with teriparatide. Each was informed that details of their case would be submitted for publication. METHODS Retrospective case analysis. RESULTS All 3 patients experienced both rapid clinical improvement and computed tomography evidence of fracture union. CONCLUSION These 3 cases represent relatively uncommon clinical scenarios in which type III odontoid fractures in osteoporotic women failed to unite with external immobilization over several months. The patients presented for follow-up with substantial, activity-limiting neck pain. All 3 were begun on teriparatide doses therapeutic for osteoporosis, and all 3 experienced both remarkable resolution of chronic neck pain and computed tomography-confirmed union of the fractures.
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Yang H, Wang G, Liu J, Ebraheim NA, Niu G, Hiltner L, Lee AH, Tang T. Balloon kyphoplasty in the treatment of osteoporotic vertebral compression fracture nonunion. Orthopedics 2010; 33:24. [PMID: 20055352 DOI: 10.3928/01477447-20091124-28] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Patients with nonunion of osteoporotic vertebral compression fractures that are refractory to conservative treatments have persistent back pain, progressive vertebral body collapse and kyphosis, and mobility of the fracture. Although many previous reports have reported vertebral compression fractures treated by balloon kyphoplasty, few data is available on using this method to treat nonunion of vertebral compression fractures. This study evaluated the therapeutic potential of balloon kyphoplasty in the treatment of nonunion of osteoporotic vertebral compression fractures. Twenty-one patients with nonunion of osteoporotic vertebral compression fractures were treated with balloon kyphoplasty. The criteria for diagnosis of nonunion osteoporotic vertebral compression fractures included the following: (1) history of pain for at least 6 months at the fracture site; (2) low T1- and high T2-signal on magnetic resonance images; (3) widening of fracture line on routine radiographs; and (4) movement of the endplate and changes of anterior vertebral heights on hyperextension radiographs. All patients were followed for 9 to 33 months postoperatively (mean 25 months). Statistically significant improvements in the mean postoperative anterior and middle vertebral body heights were observed compared with preoperative values. There was also statistically significant improvement in the mean values for Cobb's angle, pain (visual analog scale), and the Oswestry Disability Index at the postoperative assessment compared with the preoperative assessment. No statistically significant differences were noted between the postoperative and final follow-up assessment in any of the evaluated efficacy measures. The study suggests that balloon kyphoplasty is an effective technique to treat nonunion of osteoporotic vertebral compression fractures.
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Affiliation(s)
- Huilin Yang
- Department of Orthopedic Surgery, First Affiliated Hospital of Soochow University, Suzhou, China
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Kaback LA, Soung DY, Naik A, Geneau G, Schwarz EM, Rosier RN, O'Keefe RJ, Drissi H. Teriparatide (1-34 human PTH) regulation of osterix during fracture repair. J Cell Biochem 2008; 105:219-26. [PMID: 18494002 DOI: 10.1002/jcb.21816] [Citation(s) in RCA: 71] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Based on remarkable success of PTH as an anabolic drug for osteoporosis, case reports of off-label use of teriparatide (1-34 PTH) in patients with complicated fractures and non-unions are emerging. We investigated the mechanisms underlying PTH accelerated fracture repair. Bone marrow cells from 7 days 40 microg/kg of teriparatide treated or saline control mice were cultured and Osx and osteoblast phenotypic gene expression assessed by real-time RT-PCR in these cells. Fractured animals injected daily with either saline or 40 microg/kg of teriparatide for up to 21 days were X-rayed and histological assessment performed, as well as immunohistochemical analyses of the Osx expression in the fracture callus. Osx, Runx2 and osteoblast or chondrocyte phenotypic gene expression was also assessed in fracture calluses. Our data shows that Osx and Runx2 are up-regulated in marrow-derived MSCs isolated from mice systemically treated with teriparatide. Furthermore, these MSCs undergo accelerated osteoblast maturation compared to saline injected controls. Systemic teriparatide treatments also accelerated fracture healing in these mice concomitantly with increased Osx expression in the PTH treated fracture calluses compared to controls. Collectively, these data suggest a mechanism for teriparatide mediated fracture healing possibly via Osx induction in MSCs.
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Affiliation(s)
- Lee A Kaback
- The Center for Musculoskeletal Research, University of Rochester, Rochester, New York, USA
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Reinwald S, Weaver CM, Kester JJ. The health benefits of calcium citrate malate: a review of the supporting science. ADVANCES IN FOOD AND NUTRITION RESEARCH 2008; 54:219-346. [PMID: 18291308 DOI: 10.1016/s1043-4526(07)00006-x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
There has been considerable investigation into the health benefits of calcium citrate malate (CCM) since it was first patented in the late 1980s. This chapter is a comprehensive summary of the supporting science and available evidence on the bioavailability and health benefits of consuming CCM. It highlights the important roles that CCM can play during various life stages. CCM has been shown to facilitate calcium retention and bone accrual in children and adolescents. In adults, it effectively promotes the consolidation and maintenance of bone mass. In conjunction with vitamin D, CCM also decreases bone fracture risk in the elderly, slows the rate of bone loss in old age, and is of benefit to the health and well-being of postmenopausal women. CCM is exceptional in that it confers many unique benefits that go beyond bone health. Unlike other calcium sources that necessitate supplementation be in conjunction with a meal to ensure an appreciable benefit is derived, CCM can be consumed with or without food and delivers a significant nutritional benefit to individuals of all ages. The chemistry of CCM makes it a particularly beneficial calcium source for individuals with hypochlorydia or achlorydia, which generally includes the elderly and those on medications that decrease gastric acid secretion. CCM is also recognized as a calcium source that does not increase the risk of kidney stones, and in fact it protects against stone-forming potential. The versatile nature of CCM makes it a convenient and practical calcium salt for use in moist foods and beverages. The major factor that may preclude selection of CCM as a preferred calcium source is the higher cost compared to other sources of calcium commonly used for fortification (e.g., calcium carbonate and tricalcium phosphate). However, formation of CCM directly within beverages or other fluid foods and/or preparations, and the addition of a concentrated CCM solution or slurry, are relatively cost-effective methods by which CCM can be incorporated into finished food and beverage products.
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Affiliation(s)
- Susan Reinwald
- Department of Foods and Nutrition, Purdue University, West Lafayette, IN 47907, USA
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Lewis G, Xu J, Madigan S, Towler MR. Influence of strontia on various properties of surgical simplex P acrylic bone cement and experimental variants. Acta Biomater 2007; 3:970-9. [PMID: 17512808 DOI: 10.1016/j.actbio.2007.03.010] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2006] [Revised: 02/24/2007] [Accepted: 03/07/2007] [Indexed: 12/13/2022]
Abstract
The fact that the composition of acrylic bone cement, as used in cemented primary arthroplasties, is not optimal has been highlighted in the literature. For example: (i) deleterious effects of the radiopacifier (BaSO(4) or ZrO(2) particles in the powder) have been reported; (ii) there is an indication that pre-polymerized poly(methylmethacrylate) (PMMA) beads in the powder may be dispensed with; and (iii) there is a strong consensus that the accelerator commonly used, N,N-dimethyl-p-toluidine (DMPT), is toxic and has many other undesirable properties. At the same time, the effectiveness of drugs that contain a strontium compound in treating the effects of osteoporosis has been explained in terms of the role of strontium in bone formation and resorption. This indicates that strontium compounds may also have desirable effects on osseointegration of arthroplasties. The present study is a detailed evaluation of 24 acrylic bone cement formulations comprising different relative amounts of BaSO(4), strontia (as an alternative radiopacifier), pre-polymerized PMMA beads and DMPT. A large number of properties of the curing and cured cement were determined, including setting time, polymerization rate, fracture toughness and fatigue life. The focus was on the radiopacifier, with the finding being that many properties of formulations that contained strontia were about the same or better than those for cements that contained BaSO(4). Thus, further developmental work on strontia-containing acrylic bone cements is justified, with a view to making them candidates for use in cemented primary arthroplasties.
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Affiliation(s)
- Gladius Lewis
- Department of Mechanical Engineering, The University of Memphis, Memphis, TN 38152, USA
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Wezeman FH, Juknelis D, Himes R, Callaci JJ. Vitamin D and ibandronate prevent cancellous bone loss associated with binge alcohol treatment in male rats. Bone 2007; 41:639-45. [PMID: 17643361 PMCID: PMC2683578 DOI: 10.1016/j.bone.2007.06.002] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2006] [Revised: 05/30/2007] [Accepted: 06/04/2007] [Indexed: 12/15/2022]
Abstract
Decreased bone mass and bone strength can result from excess alcohol consumption in humans and alcohol treatment in the rat. Although the specific mechanism is unknown, the damaging effects of alcohol abuse modulate the bone remodeling cycle and increase bone turnover. Chronic alcohol consumption models have shown an inhibition of bone formation. We previously reported that binge alcohol treatment increases bone resorption and that alcohol-induced damage can be prevented by treatments with intermittent parathyroid hormone and bisphosphonates. In this study, we hypothesized that an effective dose of vitamin D (cholecalciferol) or a single dose of ibandronate would prevent bone loss caused by binge alcohol treatment in male rats. Forty-eight adult (450 gram) male Sprague-Dawley rats were randomly assigned to 6 treatment groups (n=8): (a) saline i.p., 3 days/week (C); (b) binge alcohol, 3 g/kg i.p., 3 days/week (A); (c) vitamin D, 5,000 IU/kg daily s.c. (D); (d) binge alcohol and vitamin D (AD); (e) ibandronate (120 microg, given as a single i.p. injection (I)); and (f) alcohol and ibandronate (AI) . After 4 weeks of treatment, proximal tibia and L3 and L4 vertebrae were analyzed for bone mineral density (BMD) by quantitative computerized tomography and compressive strength-to-failure using an Instron materials testing machine. Type I collagen cross-linked c-telopeptide, calcium, and 25-OH vitamin D levels were measured in serum collected at the time of sacrifice. Binge alcohol significantly decreased cancellous BMD by 58% in tibia and 23% in lumbar spine (p<0.05). Binge alcohol treatment decreased L3 and L4 compressive strength-to-failure by 21% (p<.05). Treatment with vitamin D at 5,000 IU/kg/day prevented alcohol-induced bone loss, significantly increasing both tibial and vertebral cancellous BMD values (161% increase in tibia and 40% increase in vertebra, respectively, p<0.05) compared to alcohol alone groups. Pre-treatment with the single dose of 120 microg ibandronate prevented alcohol-induced bone loss, increasing cancellous BMD by 186% in tibiae and by 46% in vertebrae compared to the alcohol alone group (p<0.05). In summary, binge alcohol-induced tibial and vertebral bone loss can be prevented using an effective dose of vitamin D or a single dose of ibandronate even during high blood alcohol concentrations that have been shown to impair osteoblast functions and increase bone resorption.
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Affiliation(s)
- Frederick H Wezeman
- Department of Orthopaedic Surgery and Rehabilitation, and the Alcohol Research Program, Loyola University Stritch School of Medicine, 2160 So. First Ave., Maywood, Illinois 60153, USA.
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16
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Genuis SJ, Schwalfenberg GK. Picking a bone with contemporary osteoporosis management: Nutrient strategies to enhance skeletal integrity. Clin Nutr 2007; 26:193-207. [PMID: 17046114 DOI: 10.1016/j.clnu.2006.08.004] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2006] [Revised: 08/14/2006] [Accepted: 08/27/2006] [Indexed: 12/31/2022]
Abstract
Epidemic rates of osteoporosis in the western world have yielded intense efforts to develop management approaches to combat this potentially devastating disorder; recent research has unveiled innovative strategies which hold considerable promise for prevention of skeletal compromise and amelioration of suboptimal bone health. According to many algorithms and practice directives, the contemporary assessment and management of osteoporosis focuses heavily on determination of fracture risk and pharmaceutical intervention for those patients deemed to be at high risk. While routine recommendations for calcium and vitamin D have been incorporated into most regimens, disproportionately little attention has been given to recent research elucidating improved bone health and diminution in fracture rates experienced by patients receiving specific nutrients. In mainstream medical practice, clinical analysis and management of nutritional or dietary issues is sometimes perceived as unconventional, primitive or unsophisticated health care. Recent evidence-based research, however, supports intervention with adequate amounts of specific nutrients including vitamin D, strontium, vitamin K, and essential fatty acids in the prevention and primary management of osteoporosis.
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Affiliation(s)
- Stephen J Genuis
- University of Alberta, 2935-66 Street, Edmonton, Alberta, Canada T6K 4C1.
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17
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Lewis G. Percutaneous vertebroplasty and kyphoplasty for the stand-alone augmentation of osteoporosis-induced vertebral compression fractures: Present status and future directions. J Biomed Mater Res B Appl Biomater 2007; 81:371-86. [PMID: 17022057 DOI: 10.1002/jbm.b.30674] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Enormous research efforts are being expended on two minimally invasive procedures: percutaneous vertebroplasty (VP) and kyphoplasty (KP). The present report, which is a detailed critical review of VP and KP that emphasizes their biomechanics aspects, is divided into six parts. In the first two parts, succinct descriptions are given of osteoporosis-induced vertebral body (VB) compression fractures as the underlying pathology to be treated with VP and KP, the theory of VP and KP, and the techniques used in performing these procedures. Concerns about VP and KP, such as the high radiation exposure burden that may be imposed on both patient and medical personnel and extravasation of the injectable bone cement, are discussed in the third part. Detailed discussions of fourteen issues/questions, such as the extent to which VP or KP affects various biomechanical measures of the augmented VB and those adjacent to it and the appropriate volume of the cement to use, are presented in the fourth part. Ideas for future research, such as development of a new generation of injectable bone cements and identification of an appropriate animal model, are covered in the fifth part. The final section contains a summary of the most salient points/observations made in the report.
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Affiliation(s)
- Gladius Lewis
- Department of Mechanical Engineering, The University of Memphis, 316 Engineering Science Building, Memphis, Tennessee 38152-3180, USA.
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18
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Turner RT, Evans GL, Lotinun S, Lapke PD, Iwaniec UT, Morey-Holton E. Dose-response effects of intermittent PTH on cancellous bone in hindlimb unloaded rats. J Bone Miner Res 2007; 22:64-71. [PMID: 17042715 DOI: 10.1359/jbmr.061006] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
UNLABELLED HLU suppressed bone formation and resulted in bone loss in the tibial metaphysis of 6-month-old male rats. A human therapeutic dose of intermittent PTH (1 microg/kg/day) prevented the skeletal changes associated with HLU. INTRODUCTION Skeletal unloading of skeletally mature rats results in trabecular thinning in the proximal tibial metaphysis, which is in part caused by a decrease in bone formation. We examined the efficacy of PTH in preventing the detrimental skeletal effects that occur with hindlimb unloading (HLU). MATERIALS AND METHODS Six-month-old male Fisher 344 rats were HLU and treated with vehicle or recombinant human PTH(1-34) at 1, 5, 20, or 80 microg/kg/day for 2 weeks. The bone response was measured by microCT analysis of bone structure, histomorphometric analysis of static and dynamic bone parameters, and Northern blot analysis of mRNA levels for bone matrix proteins. The PTH-treated HLU animals were compared with vehicle-treated HLU and pair-fed normal weight-bearing controls. RESULTS Unloading resulted in a decrease in cancellous bone volume that was caused in part by a dramatic 83% decrease in bone formation. All dose rates (1-80 microg/kg/day) of human PTH(1-34) significantly increased bone formation rates compared with vehicle-treated HLU controls. There was a dose response, and the highest dose rate of the hormone increased bone formation compared with normal weight-bearing rats by 708% (p < 0.0001). The increases in bone formation were accompanied by increases in mRNA levels for type 1 collagen, osteocalcin, and osteonectin. Also, treatment with PTH resulted in increases in mineral apposition rate and double-labeled perimeter, but the latter was disproportionally increased at high dose rates. A therapeutic dose of PTH (1 microg/kg/day) prevented disuse-induced trabecular thinning, whereas high-dose PTH (80 microg/kg/day) increased trabecular thickness compared with normal weight-bearing rats. CONCLUSIONS These findings reveal that administration of a therapeutic dose of PTH to HLU rats prevents the decrease in bone formation and trabecular thinning, whereas high dose rates of the hormone increase bone formation and trabecular thickness to values that exceed normal values.
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Affiliation(s)
- Russell T Turner
- Department of Nutrition and Exercise, Oregon State University, Corvallis, OR 97330, USA.
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19
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Abstract
Osteoporosis, as defined by the National Osteoporosis Foundation, is a disease that is characterized by low bone mass and structural deterioration of bone tissue, which leads to bone fragility and an increased susceptibility to fractures. Aging is only one factor that contributes to the development of osteoporosis. Genetics, suboptimal nutrition, deficiency of calcium and vitamin D, lifestyle, smoking, decrease in sex hormone production, and medications also contribute to skeletal fragility. Osteoporotic fractures are a frequent and important cause of disability and medical costs worldwide. Fortunately, osteoporotic fractures are preventable. Several guidelines for the prevention, screening, diagnosis, and management for osteoporosis have been established. Although some are consistent and similar, others are not.
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Affiliation(s)
- Milisa K Rizer
- Department of Family Medicine, The Ohio State University, 2231 North High Street, Columbus, OH 43201, USA.
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20
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Trumm CG, Jakobs TF, Zech CJ, Weber C, Reiser MF, Hoffmann RT. [Vertebroplasty in the treatment of back pain]. Radiologe 2006; 46:495-505. [PMID: 16786386 DOI: 10.1007/s00117-006-1382-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
BACKGROUND Percutaneous vertebroplasty (PVP) represents a minimally invasive option which is gaining in importance for the treatment of vertebral compression fractures (VCF) and osteolysis of the spine. This article describes the indications for its use, peri-interventional imaging, technique, and results of PVP. MATERIAL AND METHODS The current guidelines for performance of PVP are explained in accordance with the "Interdisciplinary Consensus Paper on Vertebroplasty and Kyphoplasty" of the German Professional Associations and the 2005 CIRSE Guidelines. The results of our own study carried out in 2002 are compared to the complication rates and clinical outcomes reported in the literature. RESULTS Painful osteoporotic VCF and osteolysis within the vertebral body due to metastases and multiple myeloma are indications for PVP. Absolute contraindications are, in particular, asymptomatic VCF, alleviation of pain by drug treatment, therapy-refractory coagulopathies, allergies to cement components, and active infections. MRI or CT is indicated before undertaking PVP to assess the fracture age, to exclude other causes of pain, and to evaluate the posterior edge of the vertebral body. High-quality mono- or biplanar fluoroscopy--preferably in combination with CT (fluoroscopy)--is necessary for PVP to minimize the risk of cement leakage. A clear reduction in pain [mean reduction of 6.1 points (VAS)] is achieved in 86-92% of the patients with PVP. Our own study treating 58 patients (mean follow-up 323+/-99 days) revealed a clear alleviation of pain in 77% [-5.7 points (VAS)]. CONCLUSION PVP constitutes a safe and effective minimally invasive treatment approach to stabilize and reduce acute and chronic back pain due to osteoporotic VCF and tumor-associated osteolysis.
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Affiliation(s)
- C G Trumm
- Institut für Klinische Radiologie, Klinikum Grosshadern der Ludwig-Maximilians-Universität, Marchioninistrasse 15, 81377 München.
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21
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Heran MKS, Legiehn GM, Munk PL. Current concepts and techniques in percutaneous vertebroplasty. Orthop Clin North Am 2006; 37:409-34, vii. [PMID: 16846770 DOI: 10.1016/j.ocl.2006.05.001] [Citation(s) in RCA: 36] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Percutaneous vertebroplasty is a safe and effective alternative for the treatment of many different types of painful vertebral lesions, including osteoporotic compression fractures,hemangiomas, or malignancy-induced pathologic vertebral fractures. Medical therapy often is limited to pain control and immobilization. Because surgery is contraindicated frequently in patients who have osteoporotic compression fractures, and because patients who have widespread metastatic disease often are not surgical candidates, vertebroplasty may be the only practical option. In experienced hands and with appropriately selected patients, percutaneous vertebroplasty is a safe, inexpensive, and highly efficacious procedure; however, because of the potential for devastating complications, all efforts must be made to optimize patient safety.
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Affiliation(s)
- Manraj K S Heran
- Department of Radiology, Division of Neuroradiology, Vancouver General Hospital, University of British Columbia, 899 West 12th Avenue, Vancouver, British Columbia, V5Z 1M9, Canada.
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Abstract
It has been many years since bone loss and fracture risk were first recognized as serious complications of stroke. Hip fracture is associated with a substantial increase in morbidity and mortality for stroke survivors, and therefore, assessing and maintaining skeletal health after stroke should be an important clinical goal. Recent long-term, prospective studies have illustrated a highly nonuniform pattern of bone changes after stroke. In general, there is significant bone loss on the paretic side, which is greatest in those patients with the most severe functional deficits. In some patients, bone loss in the paretic arm during the first year after stroke is the equivalent of >20 yrs of bone loss in healthy individuals of comparable age. Bone density in the nonparetic upper limb can actually increase after stroke, consistent with an increase in habitual use of the nonparetic hand. Bone density in the paretic lower limb can decrease by >10% in <1 yr, with smaller decreases being typical for the nonparetic lower limb. Despite the recent increase in the number of prospective, longitudinal studies, important questions about bone changes after stroke remain unanswered. Longer-term studies quantifying bone loss for periods of >12 mos poststroke are needed to determine how long excess bone loss continues after stroke. Studies with more subjects and with more varied disability levels are needed to better understand the relationships between functional deficits and bone loss. New metrics are needed to quantify the intensity and duration of physical activity in the upper and lower limbs that are consistent with previous research on the role of mechanical stimuli in bone adaptation. Finally, an assessment of skeletal health and the factors that affect bone quantity and quality should be a standard component in the clinical management of all survivors of stroke.
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Affiliation(s)
- Gary S Beaupre
- Bone and Joint Center of Excellence, VA Palo Alto Health Care System, Palo Alto 94304, and the Biomechanical Engineering, Stanford University, Stanford, California, USA
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Kung AWC, Pasion EG, Sofiyan M, Lau EMC, Tay BK, Lam KS, Wilawan K, Ongphiphadhanakul B, Thiebaud D. A comparison of teriparatide and calcitonin therapy in postmenopausal Asian women with osteoporosis: a 6-month study. Curr Med Res Opin 2006; 22:929-37. [PMID: 16709314 DOI: 10.1185/030079906x104768] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
OBJECTIVE The number of hip fractures is expected to double in the next 20 years, with current estimates that Asia will account for 37% of these cases. As bone mineral density (BMD) may be used as a measure of fracture risk, we sought to compare the effects of teriparatide with salmon calcitonin treatment on changes in BMD, biochemical bone markers, and safety in postmenopausal Asian women with osteoporosis. METHODOLOGY A total of 104 patients (n = 47 teriparatide [20 g/day subcutaneously] and n = 57 calcitonin [100 IU/day subcutaneously]) were enrolled in Hong Kong, Singapore, Philippines, Malaysia, and Thailand. Calcium (> or = 500 mg/day) and vitamin D (200-400 IU/day) supplements were taken throughout the 6-month controlled, randomized study. RESULTS Teriparatide was associated with a 5.03 +/- 4.77% increase in lumbar spine BMD (p < 0.0001, mean +/- SD change from baseline), whereas changes in lumbar spine BMD for patients on calcitonin were not statistically significant (mean change of 0.36 +/- 4.12%, p = 0.16). Comparison of the two groups indicated that teriparatide treatment improved lumbar spine BMD statistically significantly more than calcitonin (p < 0.0001). No statistically significant changes were observed for total hip or femoral neck BMD. Serum bone-specific alkaline phosphatase (BSAP) increased by 55.9% (median change from baseline, p < 0.0001) in the teriparatide group, and remained stable with calcitonin (5.0% change, p = 0.24); osteocalcin increased by 156.15% (median change from baseline, p < 0.0001) with teriparatide, and decreased with calcitonin (-15.25%, p = 0.03). Similar rates of adverse events were observed, with nausea and dizziness the most commonly reported for both groups (teriparatide versus calcitonin, 13.0% versus 23.2% p = 0.21, 10.9% versus 21.4% p = 0.19, respectively). There were no clinically relevant changes observed in laboratory parameters. CONCLUSIONS Both treatments were similarly tolerated, however teriparatide was associated with greater increases in lumbar spine BMD and bone formation markers, demonstrating the unique mechanism of action and safety of this treatment for osteoporosis in these Asian women.
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Affiliation(s)
- A W C Kung
- Dept of Medicine, University of Hong Kong, Queen Mary Hospital, China
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Karlin BE, Duffy M. Geriatric Mental Health Policy: Impact on Service Delivery and Directions for Effecting Change. ACTA ACUST UNITED AC 2004. [DOI: 10.1037/0735-7028.35.5.509] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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