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European Review For Medical and... May 2021Osteoporosis is a metabolic disease of the skeletal system which currently affects over 200 million patients worldwide. The WHO criteria define osteoporosis as low bone... (Review)
Review
Osteoporosis is a metabolic disease of the skeletal system which currently affects over 200 million patients worldwide. The WHO criteria define osteoporosis as low bone mineral density, with a T-score ≤ -2.5 found in the spine, the neck of the femur, or during a full hip examination. Osteoporosis considerably reduces a patient's quality of life. QoL should be carefully evaluated before fractures occur to enable the development of an appropriate treatment plan. The progression of osteoporosis may be significantly inhibited by following a proper diet, leading a healthy lifestyle, taking dietary supplements, and receiving appropriate treatment. Education and the prevention of the disease play a major role. Potentially modifiable risk factors for osteoporosis are vitamin D deficiency, smoking, alcohol consumption, low calcium intake, low or excessive phosphorus intake, protein deficiency or a high-protein diet, excessive consumption of coffee, a sedentary lifestyle or lack of mobility, and insufficient exposure to the sun. Pharmaceutical treatment for osteoporosis involves bisphosphonates, calcium and vitamin D3, denosumab, teriparatide, raloxifene, and strontium ranelate. Data indicates that 30%-50% of patients do not take their medication correctly. Other methods of treatment include exercise, kinesitherapy, treatment at a health resort, physical therapy, and diet.
Topics: Cholecalciferol; Denosumab; Dietary Supplements; Diphosphonates; Exercise; Humans; Kinesiology, Applied; Osteoporosis; Raloxifene Hydrochloride; Risk Factors; Teriparatide; Thiophenes
PubMed: 34002830
DOI: 10.26355/eurrev_202105_25838 -
Arthritis & Rheumatology (Hoboken, N.J.) Aug 2017To develop recommendations for prevention and treatment of glucocorticoid-induced osteoporosis (GIOP). (Review)
Review
OBJECTIVE
To develop recommendations for prevention and treatment of glucocorticoid-induced osteoporosis (GIOP).
METHODS
We conducted a systematic review to synthesize the evidence for the benefits and harms of GIOP prevention and treatment options. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of evidence. We used a group consensus process to determine the final recommendations and grade their strength. The guideline addresses initial assessment and reassessment in patients beginning or continuing long-term (≥3 months) glucocorticoid (GC) treatment, as well as the relative benefits and harms of lifestyle modification and of calcium, vitamin D, bisphosphonate, raloxifene, teriparatide, and denosumab treatment in the general adult population receiving long-term GC treatment, as well as in special populations of long-term GC users.
RESULTS
Because of limited evidence regarding the benefits and harms of interventions in GC users, most recommendations in this guideline are conditional (uncertain balance between benefits and harms). Recommendations include treating only with calcium and vitamin D in adults at low fracture risk, treating with calcium and vitamin D plus an additional osteoporosis medication (oral bisphosphonate preferred) in adults at moderate-to-high fracture risk, continuing calcium plus vitamin D but switching from an oral bisphosphonate to another antifracture medication in adults in whom oral bisphosphonate treatment is not appropriate, and continuing oral bisphosphonate treatment or switching to another antifracture medication in adults who complete a planned oral bisphosphonate regimen but continue to receive GC treatment. Recommendations for special populations, including children, people with organ transplants, women of childbearing potential, and people receiving very high-dose GC treatment, are also made.
CONCLUSION
This guideline provides direction for clinicians and patients making treatment decisions. Clinicians and patients should use a shared decision-making process that accounts for patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.
Topics: Bone Density Conservation Agents; Calcium, Dietary; Consensus; Denosumab; Diphosphonates; Glucocorticoids; Humans; Osteoporosis; Osteoporotic Fractures; Raloxifene Hydrochloride; Rheumatic Diseases; Rheumatology; Societies, Medical; Teriparatide; United States; Vitamin D
PubMed: 28585373
DOI: 10.1002/art.40137 -
Health Technology Assessment... Jun 2020Fragility fractures are fractures that result from mechanical forces that would not ordinarily result in fracture.
BACKGROUND
Fragility fractures are fractures that result from mechanical forces that would not ordinarily result in fracture.
OBJECTIVES
The objectives were to evaluate the clinical effectiveness, safety and cost-effectiveness of non-bisphosphonates {denosumab [Prolia; Amgen Inc., Thousand Oaks, CA, USA], raloxifene [Evista; Daiichi Sankyo Company, Ltd, Tokyo, Japan], romosozumab [Evenity; Union Chimique Belge (UCB) S.A. (Brussels, Belgium) and Amgen Inc.] and teriparatide [Forsteo; Eli Lilly and Company, Indianapolis, IN, USA]}, compared with each other, bisphosphonates or no treatment, for the prevention of fragility fracture.
DATA SOURCES
For the clinical effectiveness review, nine electronic databases (including MEDLINE, EMBASE and the World Health Organization International Clinical Trials Registry Platform) were searched up to July 2018.
REVIEW METHODS
A systematic review and network meta-analysis of fracture and femoral neck bone mineral density were conducted. A review of published economic analyses was undertaken and a model previously used to evaluate bisphosphonates was adapted. Discrete event simulation was used to estimate lifetime costs and quality-adjusted life-years for a simulated cohort of patients with heterogeneous characteristics. This was done for each non-bisphosphonate treatment, a strategy of no treatment, and the five bisphosphonate treatments previously evaluated. The model was populated with effectiveness evidence from the systematic review and network meta-analysis. All other parameters were estimated from published sources. An NHS and Personal Social Services perspective was taken, and costs and benefits were discounted at 3.5% per annum. Fracture risk was estimated from patient characteristics using the QFracture (QFracture-2012 open source revision 38, Clinrisk Ltd, Leeds, UK) and FRAX (web version 3.9, University of Sheffield, Sheffield, UK) tools. The relationship between fracture risk and incremental net monetary benefit was estimated using non-parametric regression. A probabilistic sensitivity analysis and scenario analyses were used to assess uncertainty.
RESULTS
Fifty-two randomised controlled trials of non-bisphosphonates were included in the clinical effectiveness systematic review and an additional 51 randomised controlled trials of bisphosphonates were included in the network meta-analysis. All treatments had beneficial effects compared with placebo for vertebral, non-vertebral and hip fractures, with hazard ratios varying from 0.23 to 0.94, depending on treatment and fracture type. The effects on vertebral fractures and the percentage change in bone mineral density were statistically significant for all treatments. The rate of serious adverse events varied across trials (0-33%), with most between-group differences not being statistically significant for comparisons with placebo/no active treatment, non-bisphosphonates or bisphosphonates. The incremental cost-effectiveness ratios were > £20,000 per quality-adjusted life-year for all non-bisphosphonate interventions compared with no treatment across the range of QFracture and FRAX scores expected in the population eligible for fracture risk assessment. The incremental cost-effectiveness ratio for denosumab may fall below £30,000 per quality-adjusted life-year at very high levels of risk or for high-risk patients with specific characteristics. Raloxifene was dominated by no treatment (resulted in fewer quality-adjusted life-years) in most risk categories.
LIMITATIONS
The incremental cost-effectiveness ratios are uncertain for very high-risk patients.
CONCLUSIONS
Non-bisphosphonates are effective in preventing fragility fractures, but the incremental cost-effectiveness ratios are generally greater than the commonly applied threshold of £20,000-30,000 per quality-adjusted life-year.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42018107651.
FUNDING
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 24, No. 29. See the NIHR Journals Library website for further project information.
Topics: Bone Density Conservation Agents; Clinical Trials as Topic; Cost-Benefit Analysis; Denosumab; Diphosphonates; Humans; Osteoporotic Fractures; Quality-Adjusted Life Years; Raloxifene Hydrochloride; Teriparatide; Treatment Outcome
PubMed: 32588816
DOI: 10.3310/hta24290 -
Annals of Internal Medicine Jun 2017This guideline updates the 2008 American College of Physicians (ACP) recommendations on treatment of low bone density and osteoporosis to prevent fractures in men and...
DESCRIPTION
This guideline updates the 2008 American College of Physicians (ACP) recommendations on treatment of low bone density and osteoporosis to prevent fractures in men and women. This guideline is endorsed by the American Academy of Family Physicians.
METHODS
The ACP Clinical Guidelines Committee based these recommendations on a systematic review of randomized controlled trials; systematic reviews; large observational studies (for adverse events); and case reports (for rare events) that were published between 2 January 2005 and 3 June 2011. The review was updated to July 2016 by using a machine-learning method, and a limited update to October 2016 was done. Clinical outcomes evaluated were fractures and adverse events. This guideline focuses on the comparative benefits and risks of short- and long-term pharmacologic treatments for low bone density, including pharmaceutical prescriptions, calcium, vitamin D, and estrogen. Evidence was graded according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system.
TARGET AUDIENCE AND PATIENT POPULATION
The target audience for this guideline includes all clinicians. The target patient population includes men and women with low bone density and osteoporosis.
RECOMMENDATION 1
ACP recommends that clinicians offer pharmacologic treatment with alendronate, risedronate, zoledronic acid, or denosumab to reduce the risk for hip and vertebral fractures in women who have known osteoporosis. (Grade: strong recommendation; high-quality evidence).
RECOMMENDATION 2
ACP recommends that clinicians treat osteoporotic women with pharmacologic therapy for 5 years. (Grade: weak recommendation; low-quality evidence).
RECOMMENDATION 3
ACP recommends that clinicians offer pharmacologic treatment with bisphosphonates to reduce the risk for vertebral fracture in men who have clinically recognized osteoporosis. (Grade: weak recommendation; low-quality evidence).
RECOMMENDATION 4
ACP recommends against bone density monitoring during the 5-year pharmacologic treatment period for osteoporosis in women. (Grade: weak recommendation; low-quality evidence).
RECOMMENDATION 5
ACP recommends against using menopausal estrogen therapy or menopausal estrogen plus progestogen therapy or raloxifene for the treatment of osteoporosis in women. (Grade: strong recommendation; moderate-quality evidence).
RECOMMENDATION 6
ACP recommends that clinicians should make the decision whether to treat osteopenic women 65 years of age or older who are at a high risk for fracture based on a discussion of patient preferences, fracture risk profile, and benefits, harms, and costs of medications. (Grade: weak recommendation; low-quality evidence).
Topics: Bone Diseases, Metabolic; Calcium, Dietary; Denosumab; Diphosphonates; Estrogen Replacement Therapy; Exercise; Female; Fractures, Bone; Humans; Male; Osteoporosis; Osteoporosis, Postmenopausal; Raloxifene Hydrochloride; Risk Factors; Teriparatide; Vitamin D
PubMed: 28492856
DOI: 10.7326/M15-1361 -
Journal of Clinical Oncology : Official... Jun 2023Journal Journal of Clinical OncologyPatients with high-risk breast lesions (HRLs) or preinvasive breast cancers face an elevated risk of future breast cancer... (Review)
Review
Journal Journal of Clinical OncologyPatients with high-risk breast lesions (HRLs) or preinvasive breast cancers face an elevated risk of future breast cancer diagnoses. Endocrine therapy in this setting reduces the risk of a future diagnosis but does not confer improved survival, thus the side effects of primary/secondary prevention must be considered relative to the benefits. Here, we discuss the available chemoprevention regimens for patients with HRLs and considerations for selecting a regimen, as well as the decision making surrounding use of adjuvant endocrine therapy for patients with ductal carcinoma in situ (DCIS). For patients with HRLs, available chemoprevention regimens differ by menopausal status, including tamoxifen 20 mg once daily for 5 years and more recently tamoxifen 5 mg once daily for 3 years in both premenopausal and postmenopausal women as well as raloxifene or aromatase inhibitors for postmenopausal women. We recommend a shared decision-making approach with attention to patient preferences related to risk tolerance and side-effect profiles. Low-dose tamoxifen appears to be a particularly favorable choice that is well tolerated, without risk of serious adverse events and offers comparable risk reduction to other regimens. For DCIS, the benefit of endocrine therapy in addition to radiation is small, and appears to be driven mainly by a reduction in contralateral breast diagnoses or new breast cancers. A strategy that reduces the side-effect profile of chemoprevention such as low-dose tamoxifen may be especially appealing in the setting of secondary prevention.
Topics: Female; Humans; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Secondary Prevention; Tamoxifen; Raloxifene Hydrochloride
PubMed: 37126767
DOI: 10.1200/JCO.23.00455 -
Calcified Tissue International Jun 2023To assess the effectiveness and safety of denosumab (Prolia®) compared to bisphosphonates (alendronate, ibandronate, risedronate, zoledronate), selective estrogen... (Meta-Analysis)
Meta-Analysis Review
The Clinical Effectiveness of Denosumab (Prolia®) for the Treatment of Osteoporosis in Postmenopausal Women, Compared to Bisphosphonates, Selective Estrogen Receptor Modulators (SERM), and Placebo: A Systematic Review and Network Meta-Analysis.
To assess the effectiveness and safety of denosumab (Prolia®) compared to bisphosphonates (alendronate, ibandronate, risedronate, zoledronate), selective estrogen receptor modulators (SERMs; bazedoxifene, raloxifene) or placebo, for the treatment of osteoporosis in postmenopausal women (PMW). Systematic searches were run in PubMed, Embase & Cochrane Library on 27-April-2022. Randomized controlled trials (RCTs) that included osteoporotic PMW allocated to denosumab, SERMs, bisphosphonates, or placebo were eligible for inclusion. RCTs were appraised using Cochrane Risk of Bias 2.0. Bayesian network and/or pairwise meta-analyses were conducted on predetermined outcomes (i.e. vertebral/nonvertebral fractures, bone mineral density [BMD], mortality, adverse events [AEs], serious AEs (SAEs), withdrawals due to AEs, AEs caused by denosumab discontinuation). A total of 12 RCTs (k = 22 publications; n = 25,879 participants) were included in the analyses. Denosumab, reported a statistically significant increase in lumbar spine (LS) and total hip (TH) BMD, compared to placebo. Similarly, denosumab also resulted in a statistically significant increase in TH BMD compared to the raloxifene and bazedoxifene. However, relative to denosumab, alendronate, ibandronate and risedronate resulted in significant improvements in both femoral neck (FN) and LS BMD. With regards to vertebral fractures and all safety outcomes, there were no statistically significant differences between denosumab and any of the comparator. Relative to placebo, denosumab was associated with significant benefits in both LS and TH BMD. Additionally, denosumab (compared to placebo) was not associated with reductions in vertebral and nonvertebral fractures. Finally, denosumab was not associated with improvement in safety outcomes, compared to placebo. These findings should be interpreted with caution as some analyses suffered from statistical imprecision.
Topics: Female; Humans; Diphosphonates; Selective Estrogen Receptor Modulators; Denosumab; Alendronate; Bone Density Conservation Agents; Risedronic Acid; Raloxifene Hydrochloride; Ibandronic Acid; Network Meta-Analysis; Postmenopause; Osteoporosis, Postmenopausal; Osteoporosis; Bone Density; Spinal Fractures; Treatment Outcome
PubMed: 37016189
DOI: 10.1007/s00223-023-01078-z -
EBioMedicine Dec 2023Drug repurposing provides a cost-effective approach to address the need for breast cancer prevention and therapeutics. We aimed to identify actionable druggable targets...
BACKGROUND
Drug repurposing provides a cost-effective approach to address the need for breast cancer prevention and therapeutics. We aimed to identify actionable druggable targets using Mendelian randomization (MR) and then validate the candidate drugs using population-based analyses.
METHODS
We identified genetic instruments for 1406 actionable targets of approved non-oncological drugs based on gene expression, DNA methylation, and protein expression quantitative trait loci (eQTL, mQTL, and pQTL, respectively). Genome-wide association study (GWAS) summary statistics were obtained from the Breast Cancer Association Consortium (122,977 cases, 105,974 controls). We further conducted a nested case-control study using data retrieved from Swedish registers to validate the candidate drugs that were identified from MR analyses.
FINDINGS
We identified six significant MR associations with gene expression levels (TUBB, MDM2, CSK, ULK3, MC1R and KCNN4) and two significant associations with gene methylation levels across 21 CpG islands (RPS23 and MAPT). Results from the nested case-control study showed that the use of raloxifene (targeting MAPT) was associated with 35% reduced breast cancer risk (odds ratio, OR, 0.65; 95% confidence interval, CI, 0.51-0.83). However, usage of estradiol, tolterodine, and nitrofurantoin (also targeting MAPT) was associated with increased breast cancer risk, with adjusted ORs and 95% CI of 1.10 (1.07-1.13), 1.16 (1.09-1.24), and 1.09 (1.05-1.13), respectively. The effect of raloxifene and nitrofurantoin lost significance in further validation analyses using active-comparator and new-user design.
INTERPRETATION
This large-scale MR analysis, combined with population-based validation, identified eight druggable target genes for breast cancer and suggested that raloxifene is an effective chemoprevention against breast cancer.
FUNDING
Swedish Research Council, Cancerfonden, Crafoordska Stiftelsen, Allmänna Sjukhusets i Malmö Stiftelsen för bekämpande av cancer, 111 Project and MAS cancer.
Topics: Humans; Female; Breast Neoplasms; Case-Control Studies; Genome-Wide Association Study; Mendelian Randomization Analysis; Nitrofurantoin; Raloxifene Hydrochloride
PubMed: 38251461
DOI: 10.1016/j.ebiom.2023.104859 -
The Journal of Clinical Endocrinology... May 2020Atypical femur fractures (AFFs) are serious adverse events associated with bisphosphonates and often show poor healing.
CONTEXT
Atypical femur fractures (AFFs) are serious adverse events associated with bisphosphonates and often show poor healing.
EVIDENCE ACQUISITION
We performed a systematic review to evaluate effects of teriparatide, raloxifene, and denosumab on healing and occurrence of AFF.
EVIDENCE SYNTHESIS
We retrieved 910 references and reviewed 67 papers, including 31 case reports, 9 retrospective and 3 prospective studies on teriparatide. There were no RCTs. We pooled data on fracture union (n = 98 AFFs on teriparatide) and found that radiological healing occurred within 6 months of teriparatide in 13 of 30 (43%) conservatively managed incomplete AFFs, 9 of 10 (90%) incomplete AFFs with surgical intervention, and 44 of 58 (75%) complete AFFs. In 9 of 30 (30%) nonoperated incomplete AFFs, no union was achieved after 12 months and 4 (13%) fractures became complete on teriparatide. Eight patients had new AFFs during or after teriparatide. AFF on denosumab was reported in 22 patients, including 11 patients treated for bone metastases and 8 without bisphosphonate exposure. Denosumab after AFF was associated with recurrent incomplete AFFs in 1 patient and 2 patients of contralateral complete AFF. Eight patients had used raloxifene before AFF occurred, including 1 bisphosphonate-naïve patient.
CONCLUSIONS
There is no evidence-based indication in patients with AFF for teriparatide apart from reducing the risk of typical fragility fractures, although observational data suggest that teriparatide might result in faster healing of surgically treated AFFs. Awaiting further evidence, we formulate recommendations for treatment after an AFF based on expert opinion.
Topics: Bone Density Conservation Agents; Denosumab; Diphosphonates; Europe; Femoral Fractures; Humans; Osteoporotic Fractures; Practice Patterns, Physicians'; Raloxifene Hydrochloride; Risk Assessment; Risk Factors; Societies, Medical; Teriparatide
PubMed: 31867670
DOI: 10.1210/clinem/dgz295 -
Breast Cancer Research and Treatment Sep 2023Chemoprevention with a selective estrogen receptor modulator (tamoxifen or raloxifene) is a non-surgical option offered to high-risk women to reduce the risk of breast...
PURPOSE
Chemoprevention with a selective estrogen receptor modulator (tamoxifen or raloxifene) is a non-surgical option offered to high-risk women to reduce the risk of breast cancer. The evidence for tamoxifen benefit is based on trials conducted among predominantly postmenopausal women from the general population and on studies of contralateral breast cancer in women with a pathogenic variant (mutation hereafter) in BRCA1 or BRCA2. Tamoxifen has not been assessed as a primary prevention agent in women with an inherited BRCA mutation.
METHODS
We conducted a prospective analysis of tamoxifen chemoprevention and the risk of breast cancer in women with a BRCA1 or BRCA2 mutation. Data on tamoxifen (and raloxifene) use was collected by questionnaire and updated biennially. Information on incident cancers was collected by self-report and was confirmed by medical record review. In a matched analysis, we estimated the hazard ratio (HR) and 95% confidence intervals (CI) for developing a first primary breast cancer associated with tamoxifen or raloxifene use, using Cox proportional hazards analysis.
RESULTS
There were 4578 unaffected women in the cohort, of whom 137 reported tamoxifen use (3%), 83 reported raloxifene use (2%) and 12 used both drugs (0.3%). Women who used tamoxifen or raloxifene were matched 1:3 with women who used neither drug on year of birth, country of residence, year of study entry and gene (BRCA1 or BRCA2). We generated 202 matched pairs. After a mean follow-up of 6.8 years, there were 22 incident breast cancers diagnosed among tamoxifen/raloxifene users (10.9% of users) and 71 cases diagnosed among non-users (14.3% of non-users; HR = 0.64; 95% CI 0.40-1.03; P = 0.07).
CONCLUSION
Chemoprevention may be an effective risk-reduction option for BRCA mutation carriers, but further studies with longer follow-up are necessary.
Topics: Humans; Female; Tamoxifen; Breast Neoplasms; Raloxifene Hydrochloride; Genes, BRCA1; Mutation; Risk Factors; BRCA1 Protein; BRCA2 Protein
PubMed: 37432545
DOI: 10.1007/s10549-023-06991-3 -
Journal of Midwifery & Women's Health May 2019Osteoporosis is described as a silent disease prior to fracture, and the sequelae of an osteoporotic fracture can be devastating. Primary care providers should routinely... (Review)
Review
Osteoporosis is described as a silent disease prior to fracture, and the sequelae of an osteoporotic fracture can be devastating. Primary care providers should routinely assess and remediate bone health during wellness visits for women aged at least 50 years. Assessment includes review of a variety of risk factors, bone density testing, and an online fracture risk assessment tool calculation. Diagnosis is based on bone density score and clinical risk factors. Evidence-based nonpharmacologic therapies are important adjuncts of care, and pharmacologic intervention may also be recommended. A variety of pharmacologic options are available for women with postmenopausal osteoporosis, and it is important to weigh benefits and risks. Pharmacologic indications, therapeutic variations among products, adverse effect profiles, administration considerations, and cost are addressed. Once pharmacotherapy is initiated, duration and drug holidays should also be considered. In general, medication benefits fade when treatment stops, so health care providers should be prepared to routinely revisit therapy indicators that will help define risk and guide treatment decisions. A comprehensive approach to bone health can make a valuable difference in the health of women.
Topics: Absorptiometry, Photon; Aged; Bone Density Conservation Agents; Calcitonin; Denosumab; Diagnostic Screening Programs; Diphosphonates; Drug Therapy; Estrogen Replacement Therapy; Evidence-Based Medicine; Female; Health Status Indicators; Humans; Middle Aged; Osteoporosis, Postmenopausal; Raloxifene Hydrochloride; Risk Assessment; Risk Factors; Teriparatide; Vitamins
PubMed: 30869832
DOI: 10.1111/jmwh.12954