warfarin and Osteoporosis

Evidence on the association between the risk of new-onset osteoporosis and oral anticoagulants remains controversial. We aimed to compare the risk of osteoporosis associated with the use of direct oral anticoagulants (DOACs) with that associated with warfarin use.. Studies published up to 15 March 2023 that investigated the association between the use of DOACs and warfarin and the incidence of osteoporosis were identified by online searches in PubMed, Embase, the Cochrane Library, and Web of Science conducted by two independent investigators. Random-effects or fixed-effect models were employed to synthesize hazard ratios (HRs)/relative ratios (RRs) with 95% confidence intervals (CIs) for estimating the risk of osteoporosis correlated with DOAC and warfarin prescriptions (PROSPERO No. CRD42023401199).. Our meta-analysis ultimately included four studies involving 74,338 patients. The results suggested that DOAC use was associated with a significantly lower incidence of new-onset osteoporosis than warfarin use (pooled HR: 0.71, 95% CI: 0.57 to 0.88,. DOAC users experienced a lower incidence of osteoporosis than warfarin users. This study may give us insight into safe anticoagulation strategies for patients who are at high risk of developing osteoporosis.. https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023401199.

Topics: Anticoagulants; Atrial Fibrillation; Female; Hemorrhage; Humans; Male; Osteoporosis; Stroke; Warfarin

Many drugs influence fracture risk besides glucocorticoid, a most common cause of drug-induced osteoporosis. It is well established that drugs used for anti-sex steroids therapy for breast and prostate cancers increase fracture risk, including GnRH agonists, aromatase inhibitors, and anti-androgens. Increased fracture risk is also established with anti-diabetic thiazolidinediones by a randomized control study as well as meta analysis of observational studies. Multiple observational studies have indicated increased fracture risks with selective serotonin reuptake inhibitors and proton pump inhibitors. Excess thyroid hormones, anti epileptics, heparin, warfarin, may also be associated with an increase in fracture risks. On the contrary, statins, thiazides, beta blockers, and nitrates may be associated with decreased fracture risks.

Topics: Adrenergic beta-Antagonists; Androgen Antagonists; Anticonvulsants; Aromatase Inhibitors; Fractures, Spontaneous; Glucocorticoids; Gonadotropin-Releasing Hormone; Heparin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemic Agents; Nitrates; Osteoporosis; Proton Pump Inhibitors; Risk; Selective Serotonin Reuptake Inhibitors; Sodium Chloride Symporter Inhibitors; Thiazolidinediones; Thyroid Hormones; Warfarin

Topics: Administration, Oral; Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Drug Contamination; Drug Monitoring; Food-Drug Interactions; Hemorrhage; Heparin; Humans; Hypersensitivity; Injections, Subcutaneous; Necrosis; Osteoporosis; Skin Diseases; Subcutaneous Tissue; Thrombocytopenia; Warfarin

Involutional osteoporosis is one of common diseases related to ageing. However, it is essential for physicians to exclude possibilities that it is caused by certain background diseases or disorders, such as hypercortisolism, hyperthyroidism and type 1 diabetes mellitus. In addition, there are several diseases other than osteoporosis, that are known to be associated with low bone mineral density, although osteoporosis is usually diagnosed according to bone mineral density measurements. Thus, physicians should be prepared to appropriately evaluate how bone metabolism is impaired in the face of patients with low bone mineral density.

Topics: Anticonvulsants; Antidepressive Agents; Bone and Bones; Bone Density; Cushing Syndrome; Diabetes Mellitus, Type 1; Glucocorticoids; Humans; Hyperthyroidism; Neoplasms; Osteoporosis; Warfarin

Arteriosclerosis, characterized by remodeling and stiffening of large elastic arteries is the most significant manifestation of vascular aging. The increased stiffening is believed to originate from a gradual mechanical senescence of the elastic network, alterations in cross-linking of extracellular matrix components, fibrosis and calcification of elastic fibers (medial elastocalcinosis). The stiffening of large arteries reduces their capacitance and accelerates pulse wave velocity, thus contributing to a widening of pulse pressure and to the increased prevalence of isolated systolic hypertension with age. Current antihypertensive drugs were mainly designed to reduce peripheral resistance and are not adequate to alter the pathological process of vascular stiffening or even to selectively reduce systolic blood pressure in isolated systolic hypertension. This review puts forward the concept that elastocalcinosis is a valuable therapeutic target and presents evidence that this process can be prevented and reversed pharmacologically.

Topics: Aged; Aging; Antihypertensive Agents; Arteries; Arteriosclerosis; Calcinosis; Humans; Hypertension; Muscle, Smooth, Vascular; Osteoporosis; Systole; Vitamin K; Warfarin

Thromboembolic complications are leading causes of both maternal and fetal morbidity and mortality. To reduce the incidence of venous thromboembolism (VTE) in pregnancy and improve outcomes, a wider understanding of the risk factors involved and better identification of women at risk of thrombosis are required. Optimal management of thromboembolic disease, both to prevent VTE and to avoid recurrence of pregnancy complications such as miscarriage, centers on the use of low-molecular-weight heparin (LMWH). LMWHs, such as enoxaparin and dalteparin, have clinical and practical advantages compared with unfractionated heparin in terms of improved safety (significantly lower incidence of osteoporosis, thrombocytopenia, and possibly allergic skin reactions) and the potential for outpatient treatment of acute VTE. However, many unanswered questions remain, including who to treat, how to treat them, and when to treat in the case of patients with thrombophilia and a history of previous pregnancy complications.

Topics: Abnormalities, Drug-Induced; Adult; Contraindications; Female; Fibrinolytic Agents; Genetic Testing; Heparin; Heparin, Low-Molecular-Weight; Humans; Infant, Newborn; Maternal Age; Osteoporosis; Practice Guidelines as Topic; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Hematologic; Pregnancy Outcome; Pulmonary Embolism; Recurrence; Risk Factors; Thrombocytopenia; Thrombolytic Therapy; Thrombophilia; Thrombophlebitis; Warfarin

Topics: Anticoagulants; Asthma; Humans; Leukotriene Antagonists; Lung Diseases, Obstructive; Osteoporosis; Smoking Cessation; Smoking Prevention; Steroids; Warfarin

Anticoagulant therapy during pregnancy is problematic because both heparin and oral anticoagulants can potentially produce adverse maternal and fetal effects. Reviewing the relevant literature makes it clear that heparin is safer for the fetus than are oral anticoagulants. For the prophylaxis and treatment of venous thromboembolic disease in pregnant patients, heparin is the preferred anticoagulant because its efficacy and safety are established. However, because the efficacy of heparin in preventing systemic embolism in patients with prosthetic heart valves is not established, either adjusted-dose heparin or a combination of heparin and oral anticoagulants can be used.

Topics: Abnormalities, Drug-Induced; Female; Fetal Diseases; Heart Valve Prosthesis; Heparin; Humans; Osteoporosis; Pregnancy; Pregnancy Complications; Pregnancy Complications, Hematologic; Thrombophlebitis; Warfarin

We aimed to compare the risk of developing osteoporosis in patients prescribed warfarin or direct-acting oral anticoagulants (DOACs) with those with no therapy.. We included 37,632 patients aged between 18 and 111 years with a recorded diagnosis of AF between 1 January 2013 and 31 December 2017. Patients were followed until the diagnosis of osteoporosis, switch or discontinuation of the OAC, last clinical visit, or end of the study period, whichever occurred first. The incidences of new-onset osteoporosis were calculated using the Cox proportional hazards model.. Of total, 16,995 (45.2%) had no recorded OAC prescription, and 20,637 had a recorded prescription of warfarin (6,609) or DOAC (14,028). Compared with those not prescribed an OAC, the risk of being diagnosed with new-onset osteoporosis increased in patients prescribed warfarin (HR 2.22, 95% CI 2.00-2.47, p < 0.001) and DOACs (HR 1.42, 95% CI 1.29-1.58, p < 0.001). However, the effect of DOACs was not statistically significant (HR 1.07, 95% CI 0.86-1.33, p < 0.535) after excluding patients with at least one recorded prescription of systemic corticosteroids, antiepileptics, or proton pump inhibitors.. Use of warfarin or DOACs was associated with a significantly increased risk of developing osteoporosis compared with no OAC treatment.

Topics: Administration, Oral; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Anticoagulants; Anticonvulsants; Atrial Fibrillation; Factor Xa Inhibitors; Humans; Middle Aged; Osteoporosis; Proton Pump Inhibitors; Retrospective Studies; Stroke; Warfarin; Young Adult

Oral anticoagulants (OAC) have shown to affect bone mineral density and cause osteoporosis. Limited studies have investigated the relationship between its use and risk of osteoporosis. We aim to compare the risk of osteoporosis in patients on warfarin versus direct oral anticoagulants (DOACs).. A retrospective single-center cohort study was conducted in veterans age > 18 years of age in whom warfarin or DOACs were newly initiated between January 1st, 2012 to April 1st, 2020 at Salem VA Medical Center. Patients on OAC for at least 90 days qualified for inclusion and excluded if they were pregnant or had history of mechanical valve and mitral stenosis, on edoxaban or had previous history of osteoporosis or use of antiosteoporosis medication. Primary outcome was comparing incidence of new-onset osteoporosis between warfarin and DOACs. Secondary outcomes included comparing incidence of all clinical fractures, hip fractures, major bleeding and intracranial bleed between the treatments. Cox proportional hazard ratios (HRs) and 95% confidence intervals (CI) comparing the two treatment groups were calculated.. A total of 1526 patients on DOAC and 1121 in warfarin group were included in the study. After propensity-score (PS) matching, 943 patients were included in each arm. Baseline characteristics were similar after PS-matching. DOAC treatment was associated with lower incidence of new-onset osteoporosis as compared to warfarin in matched cohort (aHR: 0.19, 95% CI: 0.10-0.36; p < 0.0001). The risk of all clinical fracture and hip fracture was similar in patients receiving DOACs as versus warfarin (aHR: 1.18, 95% CI: 0.82-1.69; p = 0.3671). DOAC use was associated with lower risk of major bleed (aHR: 0.07, 95% CI: 0.03-0.15; p < 0.0001) and intracranial bleed (aHR: 0.14, 95% CI: 0.03-0.64; p = 0.0111).. Overall, as compared to warfarin, prolonged use of DOACs is associated with lower risk of new-onset osteoporosis. We hope that our study findings will enlighten current clinical practices assuring safe use of OAC in veteran patients.

Topics: Administration, Oral; Adult; Anticoagulants; Atrial Fibrillation; Cohort Studies; Humans; Middle Aged; Osteoporosis; Retrospective Studies; Stroke; Veterans; Warfarin

Warfarin is prescribed to patients with atrial fibrillation (AF) for the prevention of cardioembolic complications. Whether warfarin adversely affects bone health is controversial. The availability of alternate direct oral anticoagulant (DOAC) options now make it possible to evaluate the comparative safety of warfarin in association with fracture risk.. To test the hypothesis that, among patients with nonvalvular AF, use of DOACs vs warfarin is associated with lower risk of incident fracture.. This comparative effectiveness cohort study used the MarketScan administrative claims databases to identify patients with nonvalvular AF and who were prescribed oral anticoagulants from January 1, 2010, through September 30, 2015. To reduce confounding, patients were matched on age, sex, CHA2DS2-VASc (congestive heart failure, hypertension, age [>65 years = 1 point; >75 years = 2 points], diabetes, and previous stroke/transient ischemic attack [2 points], vascular disease) score, and high-dimensional propensity scores. The final analysis included 167 275 patients with AF. Data were analyzed from February 27, 2019 to September 18, 2019.. Warfarin and DOACs (dabigatran etexilate, rivaroxaban, and apixaban).. Incident hip fracture, fracture requiring hospitalization, and all clinical fractures (identified using inpatient or outpatient claims) defined by International Classification of Diseases, Ninth Revision, Clinical Modification codes.. In the study population of 167 275 patients with AF (38.0% women and 62.0% men; mean [SD] age, 68.9 [12.5] years), a total of 817 hip fractures, 2013 hospitalized fractures, and 7294 total fractures occurred during a mean (SD) follow-up of 16.9 (13.7) months. In multivariable-adjusted, propensity score-matched Cox proportional hazards regression models, relative to new users of warfarin, new users of DOACs tended to be at lower risk of fractures requiring hospitalization (hazard ratio [HR], 0.87; 95% CI, 0.79-0.96) and all clinical fractures (HR, 0.93; 95% CI, 0.88-0.98), whereas the association with hip fractures (HR, 0.91; 95% CI, 0.78-1.07) was not statistically significant. When comparing individual DOACs with warfarin, the strongest findings were for apixaban (HR for hip fracture, 0.67 [95% CI, 0.45-0.98]; HR for fractures requiring hospitalization, 0.60 [95% CI, 0.47-0.78]; and HR for all clinical fractures, 0.86 [95% CI, 0.75-0.98]). In subgroup analyses, DOACs appeared more beneficial among patients with AF who also had a diagnosis of osteoporosis than among those without a diagnosis of osteoporosis.. In this real-world population of 167 275 patients with AF, use of DOACs-particularly apixaban-compared with warfarin use was associated with lower fracture risk. These associations were more pronounced among patients with a diagnosis of osteoporosis. Given the potential adverse effects of warfarin on bone health, these findings suggest that caution should be used when prescribing warfarin to patients with AF at high risk of fracture.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Comorbidity; Comparative Effectiveness Research; Dabigatran; Factor Xa Inhibitors; Female; Fractures, Bone; Hip Fractures; Hospitalization; Humans; Incidence; Male; Middle Aged; Osteoporosis; Proportional Hazards Models; Protective Factors; Pyrazoles; Pyridones; Rivaroxaban; Warfarin

Alendronate sodium is used to reduce the risk of bone fracture in aged osteoporosis patients. However, its side effects should be recognized, especially for those aged patients with one or more basic cardiovascular diseases.. A 90-year-old and a 75-year-old male patient were admitted to our department. These 2 patients were examined by dual energy X-ray absorptiometry (DXA).. Both patients were diagnosed with osteoporosis, they also had history of atrial fibrillation (AF) and had long term use of warfarin.. Alendronate sodium was prescribed to the two patients at 70 mg once a week.. The 2 patients had experienced dramatic increase of international normalized ratio (INR) to 4.69∼4.86 within 24 hours and gradual decrease in the next 5 days. Both patients experienced spontaneous ecchymoses and petechiae in the skin at the first 72 hours.. Alendronate sodium can transiently increase the INR over 50%, induce spontaneous ecchymoses and petechiae in the skin of aged male osteoporosis patients with AF who took warfarin. Clinicians should pay enough attention when using alendronate sodium on these kinds of patients and be aware of the consequent potential bleeding risk.

Topics: Aged; Aged, 80 and over; Alendronate; Anticoagulants; Atrial Fibrillation; Bone Density Conservation Agents; Drug Synergism; Humans; International Normalized Ratio; Male; Osteoporosis; Warfarin

Background Warfarin, a vitamin K antagonist, has been shown to affect bone mineral density and cause osteoporosis. However, studies investigating the relationship between non-vitamin K antagonist oral anticoagulants (NOACs) and osteoporosis are limited. We thus compared the risk of osteoporosis in patients with atrial fibrillation treated with either NOACs or warfarin. Methods and Results This nationwide, retrospective cohort study used Taiwan's National Health Insurance Research Database. All adult patients in Taiwan who were newly diagnosed with atrial fibrillation and treated with NOACs or warfarin between January 2012 and December 2015 were included and classified into their respective cohorts. Patients who received NOACs were subcategorized into the rivaroxaban, dabigatran, and apixaban subgroups. Propensity score matching was performed for each head-to-head comparison. Adjusted hazard ratios (aHRs) for the risk of osteoporosis were calculated using Cox proportional hazards regression models, with adjustment for confounders. Overall, 17 008 patients were included, with 8504 in each cohort. NOACs were associated with a lower osteoporosis risk than warfarin (aHR=0.82; 95% CI=0.68-0.97). A subgroup effect of treatment duration was identified (namely, the lower osteoporosis risk with NOAC compared with warfarin became stronger in those with longer treatment duration [

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Atrial Fibrillation; Dabigatran; Databases, Factual; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Osteoporosis; Pyrazoles; Pyridones; Retrospective Studies; Risk Assessment; Risk Factors; Rivaroxaban; Taiwan; Treatment Outcome; Warfarin

Topics: Adverse Drug Reaction Reporting Systems; Anticoagulants; Confidence Intervals; Data Mining; Databases, Factual; Female; Humans; Male; Osteoporosis; Sex Characteristics; Warfarin

In recent years, direct oral anticoagulants (DOACs) of dabigatran, rivaroxaban, apixaban, edoxaban, which are all alternatives to warfarin, have been released. The use of DOACs is becoming more widespread in the clinical management of thrombotic stroke risk in patients with atrial fibrillation (AF). In large-scale clinical trials of each drug, DOACs were reported to inhibit intracranial hemorrhage, stroke, and death compared to warfarin. Warfarin is an endogenous vitamin K antagonist; therefore, patients who are taking warfarin must be prohibited from taking vitamin K. Vitamin K is an essential cofactor required for the ɤ-carboxylation of vitamin K-dependent proteins including coagulation factors, osteocalcin (OC), matrix Gla protein (MGP), and the growth arrest-specific 6 (GAS6). OC is a key factor for bone matrix formation. MGP is a local inhibitor of soft tissue calcification in the vessel wall. GAS6 prevents the apoptosis of vascular smooth muscle cells. Therefore, decrease of blood vitamin K levels may cause osteoporosis, vascular calcification, and the inhibition of vessels angiogenesis. This study aimed to evaluate the effects of changing from warfarin to rivaroxaban on bone mineral metabolism, vascular calcification, and vascular endothelial dysfunction. We studied 21 consecutive patients with persistent or chronic AF, who were treated with warfarin at least for 12 months. Warfarin administration was changed to rivaroxaban (10 or 15 mg/day) in all patients. Osteopontin (OPN), bone alkaline phosphatase (BAP), and under-carboxylated osteocalcin (ucOC) were measured. Pulse wave velocity (PWV) and augmentation index (AI) were also measured as atherosclerosis assessments. All measurements were done before and six months after the rivaroxaban treatment. There was a significant increase in serum level of BAP compared to baseline (12.5 ± 4.6 to 13.4 ± 4.1 U/L, P < 0.01). In contrast, there was a significant decrease in the serum level of ucOC (9.5 ± 5.0 to 2.7 ± 1.3 ng/ml, P < 0.01). Also, in the ucOC levels, there was a significant negative correlation between baseline values and baseline to 6-months changes in high ucOC group (r = -0.97, P < 0.01). The atherosclerosis- and osteoporosis-related biomarker, serum level of OPN were significantly decreased compared to baseline (268.3 ± 46.8 to 253.4 ± 47.1 ng/ml, P < 0.01). AI and PWV were significantly decreased after 6 months of treatment with rivaroxaban (33.9 ± 18.4 to 24.7 ± 18.4%, P = 0.04; 1638.8 ± 22

Topics: Aged; Anticoagulants; Atrial Fibrillation; Biomarkers; Bone and Bones; Cytokines; Drug Substitution; Factor Xa Inhibitors; Female; Humans; Incidence; Intracranial Thrombosis; Japan; Male; Osteoporosis; Pilot Projects; Prospective Studies; Pulse Wave Analysis; Rivaroxaban; Stroke; Survival Rate; Vascular Stiffness; Warfarin

We studied bone mineral density (BMD) of children exposed to long-term warfarin. BMD Z-scores ≤ -2.0 were estimated to occur in less than one fifth of the patients after 10 years of warfarin exposure, and BMI and growth hormone deficiency predicted BMD changes over time. These predictors can help identify high-risk patients.. Children with chronic diseases are at increased risk of developing thrombosis, which may require long-term warfarin therapy. Warfarin could further jeopardize the bone health of a population already at risk for bone fragility. Our objective was to investigate the occurrence and timing of low bone mineral density (BMD) and the predictors that influence BMD trajectory in children receiving warfarin for >1 year.. We analyzed the results of an institutional protocol that includes dual-energy X-ray absorptiometry, with or without spinal X-rays and laboratory biomarkers, as required.. Low BMD (age, sex, race, and height-for-age-Z-score adjusted BMD Z-score ≤ -2.0) was detected in 13 % (9/70) of the patients at some point during their follow-up; these patients were more likely to have complex underlying medical conditions and low body mass index (BMI) percentile. BMD Z-scores remained within normal range in 87 % of children. Survival analysis showed that the estimated 10-year abnormal BMD-free rate for the entire group was 81 % (95 % confidence interval [CI] 69 to 93 %). Trajectory analysis revealed that BMI percentiles at baseline and growth hormone deficiency (GHD) were associated with lower BMD Z-scores at the first assessment, whereas baseline BMI percentile was the only predictor of BMD Z-score over time.. Our findings identified BMI and GHD as risk factors influencing BMD in children exposed to long-term warfarin, creating an opportunity for early detection and intervention in these patients.

Topics: Absorptiometry, Photon; Anticoagulants; Body Mass Index; Bone Density; Child; Child, Preschool; Disease Progression; Drug Administration Schedule; Female; Human Growth Hormone; Humans; Infant; Longitudinal Studies; Male; Osteoporosis; Osteoporotic Fractures; Retrospective Studies; Risk Factors; Warfarin

Topics: Arthritis, Rheumatoid; Bone Density Conservation Agents; Calciphylaxis; Diagnosis, Differential; Drug Therapy, Combination; Erythema Nodosum; Female; Follow-Up Studies; Humans; Middle Aged; Osteoporosis; Prednisone; Risk Assessment; Severity of Illness Index; Teriparatide; Warfarin

Osteocalcin plays a role in bone homeostasis. The vitamin K cycle is essential for the gamma-carboxylation of glutamic acid residues in osteocalcin. Some evidence suggests that long-term warfarin therapy, which inhibits the vitamin K cycle and prevents gamma-carboxylation, is associated with increased bone-fracture risk. The aim of this study was to determine the effects of warfarin and edoxaban, a direct factor Xa inhibitor, on the serum concentration of total, gamma-carboxylated (Gla-osteocalcin) and undercarboxylated osteocalcin (uc-osteocalcin) in rats.. Rats received orally administered warfarin or edoxaban, and 24h later serum and plasma were prepared. Osteocalcin level in serum was measured with ELISA. A Gla-osteocalcin was precipitated by the addition of hydroxyapatite, and the resulting supernatant was used for measuring uc-osteocalcin. Prothrombin time (PT) of plasma was also measured.. Warfarin at 1mg/kg (a dose which prolonged PT 2.62-fold) markedly increased the serum level of uc-osteocalcin and slightly increased the total osteocalcin level compared with control in rats. Serum Gla-osteocalcin significantly decreased by warfarin. Edoxaban at 1mg/kg (an antithrombotic dose) and 54mg/kg (a dose which prolonged PT 2.25-fold) had no effects on total, uc-, and Gla-osteocalcin levels.. This study demonstrates that warfarin impaired the carboxylation of osteocalcin in rats. In contrast, edoxaban at or higher doses than needed for an antithrombotic effect sustained the circulating Gla-osteocalcin level. These findings suggest that edoxaban has no effects on the production of Gla-osteocalcin and thus, may have a lower risk of adverse effects on bone health.

Topics: Administration, Oral; Animals; Anticoagulants; Blood Coagulation; Carboxylic Acids; Enzyme-Linked Immunosorbent Assay; Factor Xa; Factor Xa Inhibitors; Male; Osteocalcin; Osteoporosis; Protein Processing, Post-Translational; Prothrombin Time; Pyridines; Rats; Rats, Wistar; Risk Factors; Thiazoles; Time Factors; Vitamin K; Warfarin

This represents the fifth article in the series on yearly updates of hot topics in long term care.

Topics: Anti-Ulcer Agents; Anticoagulants; Atrial Fibrillation; Clopidogrel; Clostridioides difficile; Delirium; Diabetes Complications; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Female; Fractures, Bone; Geriatric Nursing; Humans; Male; Nursing Homes; Omeprazole; Osteoporosis; Peptic Ulcer; Platelet Aggregation Inhibitors; Pneumonia, Bacterial; Polypharmacy; Proton Pump Inhibitors; Risk Factors; Ticlopidine; Warfarin; Weight Loss

Vitamin K is an essential factor for carboxylation of bone matrix protein. Low vitamin K may be associated with reduced bone mineral density (BMD). The issue of whether long-term sodium warfarin therapy as oral anticoagulant that antagonizes vitamin K, results in decreased bone density, is controversial. Our purpose in this study was to assess the effects of warfarin on BMD.. We performed a case control study survey of bone density in 70 patients with rheumatic valvular heart disease 'mechanical valve replacement' on long-term warfarin compared with 103 randomly selected matched controls.. There was a marked reduction in BMD (g/cm(2)) and T-score of lumbar spine between patients and controls (P = 0.048, 0.005). Duration of warfarin use was the only risk factor of significant importance respectively on spinal T-score (P < 0.03).. Screening of patients on long-term warfarin for reduced bone density should be considered. We strongly suggest the prophylactic use of calcium-vitamin D supplements for these patients.

Topics: Absorptiometry, Photon; Adult; Anticoagulants; Bone Density; Case-Control Studies; Female; Femur; Health Surveys; Heart Valve Prosthesis; Humans; Lumbar Vertebrae; Male; Middle Aged; Osteoporosis; Rheumatic Heart Disease; Vitamin K; Warfarin

To determine whether warfarin use, assessed at a single point in time, is associated with bone mineral density (BMD), rates of bone loss, and fracture risk in older men.. Secondary analysis of data from a prospective cohort study.. Six U.S. clinical centers.. Five thousand five hundred thirty-three community-dwelling, ambulatory men aged 65 and older with baseline warfarin use data.. Warfarin use was assessed as current use of warfarin at baseline using an electronic medication coding dictionary. BMD was measured at the hip and spine at baseline, and hip BMD was repeated at a follow-up visit 3.4 years later. Self-reported nonspine fractures were centrally adjudicated.. At baseline, the average age of the participants was 73.6 +/- 5.9, and 321 (5.8%) were taking warfarin. Warfarin users had similar baseline BMD as nonusers (n=5,212) at the hip and spine (total hip 0.966 +/- 0.008 vs 0.959 +/- 0.002 g/cm(2), P=.37; total spine 1.079 +/- 0.010 vs 1.074 +/- 0.003 g/cm(2), P=.64). Of subjects with BMD at both visits, warfarin users (n=150) also had similar annualized bone loss at the total hip as nonusers (n=2,683) (-0.509 +/- 0.082 vs -0.421 +/- 0.019%/year, P=.29). During a mean follow-up of 5.1 years, the risk of nonspine fracture was similar in warfarin users and nonusers (adjusted hazard ratio=1.06, 95% confidence interval=0.68-1.65).. In this cohort of elderly men, current warfarin use was not associated with lower BMD, accelerated bone loss, or higher nonspine fracture risk.

Topics: Absorptiometry, Photon; Aged; Anticoagulants; Bone Density; Follow-Up Studies; Fractures, Bone; Geriatric Assessment; Health Status; Humans; Male; Multicenter Studies as Topic; Osteoporosis; Risk Factors; Warfarin

Inappropriate prescribing encompasses acts of commission i.e. giving drugs that are contraindicated or unsuitable, and acts of omission i.e. failure to prescribe drugs when indicated due to ignorance of evidence base or other irrational basis e.g. ageism. There are considerable published data on the prevalence of inappropriate prescribing; however, there are no recent published data on the prevalence of acts of omission. The aim of this study was to calculate the prevalence of acts of prescribing omission in a population of consecutively hospitalised elderly people.. A screening tool (screening tool to alert doctors to the right treatment acronym, START), devised from evidence-based prescribing indicators and arranged according to physiological systems was prepared and validated for identifying prescribing omissions in older adults. Data on active medical problems and prescribed medicines were collected in 600 consecutive elderly patients admitted from the community with acute illness to a teaching hospital. On identification of an omitted medication, the patient's medical records were studied to look for a valid reason for the prescribing omission.. Using the START list, we found one or more prescribing omissions in 57.9% of patients. In order of prevalence, the most common prescribing omissions were: statins in atherosclerotic disease (26%), warfarin in chronic atrial fibrillation (9.5%), anti-platelet therapy in arterial disease (7.3%) and calcium/vitamin D supplementation in symptomatic osteoporosis (6%).. Failure to prescribe appropriate medicines is a highly prevalent problem among older people presenting to hospital with acute illness. A validated screening tool (START) is one method of systematically identifying appropriate omitted medicines in clinical practice.

Topics: Age Factors; Aged; Aged, 80 and over; Atherosclerosis; Atrial Fibrillation; Calcium; Dietary Supplements; Evidence-Based Medicine; Guideline Adherence; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Mass Screening; Osteoporosis; Platelet Aggregation Inhibitors; Practice Patterns, Physicians'; Prevalence; Vascular Diseases; Warfarin

Topics: Aged; Anticoagulants; Complementary Therapies; Contraindications; Drug Interactions; Female; Humans; Isoflavones; Osteoporosis; Warfarin

Topics: Anticoagulants; Antifibrinolytic Agents; Humans; Osteoporosis; Risk Factors; Vitamin K; Warfarin

Vitamin K allows for gamma-carboxylation of glutamyl residues, a conversion that activates clotting factors and bone proteins. Vitamin K antagonists such as warfarin inhibit this process. Our goal was to quantify the association between warfarin and osteoporotic fractures in patients with atrial fibrillation.. This was a retrospective cohort study of Medicare beneficiaries with atrial fibrillation who were hospitalized between March 1998 and April 1999 in all 50 US states. The study outcome was osteoporotic fractures, identified by an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code for a fracture of the hip, spine, or wrist.. Compared with 7587 patients who were not prescribed warfarin, the adjusted odds ratio (OR) of fracture was 1.25 (95% confidence interval [CI], 1.06-1.48) in 4461 patients prescribed long-term warfarin therapy (> or = 1 year). The association between osteoporotic fracture and long-term warfarin use was significant in men (OR, 1.63; 95% CI, 1.26-2.10) but nonsignificant in women (OR, 1.05; 95% CI, 0.88-1.26). In 1833 patients prescribed warfarin for less than a year, the risk of osteoporotic fracture was not increased significantly (OR, 1.03). Odds ratios (95% CIs) of independent predictors of osteoporotic fractures were as follows: increasing age, 1.63 (1.47-1.80) per decade; high fall risk, 1.78 (1.42-2.21); hyperthyroidism, 1.77 (1.16-2.70); neuropsychiatric disease, 1.51 (1.28-1.78); and alcoholism, 1.50 (1.01-2.24). Factors with a reduced OR (95% CI) included African American race, 0.30 (0.18-0.51); male sex, 0.54 (0.46-0.62); and use of beta-adrenergic antagonists, 0.84 (0.70-1.00).. Long-term use of warfarin was associated with osteoporotic fractures, at least in men with atrial fibrillation. Beta-adrenergic antagonists may protect against osteoporotic fractures.

Topics: Age Distribution; Aged; Aged, 80 and over; Atrial Fibrillation; Case-Control Studies; Causality; Confidence Intervals; Female; Fractures, Spontaneous; Geriatric Assessment; Humans; Incidence; Injury Severity Score; Male; Odds Ratio; Osteoporosis; Prognosis; Reference Values; Registries; Retrospective Studies; Risk Assessment; Sex Distribution; Warfarin

Topics: Aged; Anticoagulants; Fractures, Bone; Humans; Male; Osteoporosis; Vitamin K; Warfarin

Topics: Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Fractures, Bone; Humans; Incidence; Osteoporosis; Retrospective Studies; Stroke; United States; Warfarin

The issue of whether long-term sodium warfarin therapy results in decreased bone density is controversial. To address this question, we randomized rats to once daily subcutaneous injections of either sodium warfarin (0.20 or 0.25 mg/kg) or saline for 28 days and monitored the effects on bone, both biomechanically and by histomorphometric analysis. In addition, the anticoagulant status of both saline- and warfarin-treated rats were monitored throughout the course of the experiment by measuring the prothrombin time, expressed as international normalized ratios (INRs). Rats treated with 0.25 mg/kg warfarin demonstrated INRs of approximately 2.6, while rats treated with either 0.20 mg/kg warfarin or saline were found to have INRs of 1.3 and 1.0, respectively. Biomechanical testing of the right femur of rats treated with 0.25 mg/kg warfarin demonstrated that warfarin caused an 8% reduction in bone strength as measured by maximum tolerated load. A similar reduction in the biomechanical parameters of energy to break (P<.0001) and force at break point (P<.005) was also observed. Histomorphometric analysis of the left femur of warfarin-treated rats revealed a 17% reduction in cancellous bone volume. This was accompanied by a 60% decrease in osteoblast surface, as well as an 80% reduction in osteoid surface. In contrast, warfarin treatment had the opposite effect on osteoclast surface, which was 35% higher following warfarin treatment. Based on these observations, we conclude that clinically relevant doses of warfarin decrease femoral bone strength and cancellous bone volume, both by decreasing the rate of bone formation and increasing the rate of bone resorption.

Topics: Animals; Anticoagulants; Biomechanical Phenomena; Bone Density; Bone Remodeling; Femur; Humans; Osteoblasts; Osteoclasts; Osteoporosis; Rats; Rats, Sprague-Dawley; Time Factors; Warfarin

The present experiments were carried out to test the hypothesis that artery calcification is linked to bone resorption by determining whether the selective inhibition of bone resorption with the bisphosphonates alendronate and ibandronate will inhibit artery calcification. Artery calcification was first induced by treatment of 42-day-old male rats with warfarin, a procedure that inhibits the gamma-carboxylation of matrix Gla protein and has been shown to cause extensive calcification of the artery media within 2 weeks. These experiments revealed that ibandronate (0.05 mg. kg(-1). d(-1)) and alendronate (0.1 mg x kg(-1) x d(-1)) completely inhibited calcification of all arteries and heart valves examined after 2 and 4 weeks of warfarin treatment. A 10-fold lower dose of alendronate reduced artery calcification by 50% (P<0.005). These bisphosphonate doses are comparable to those that inhibit bone resorption in rats of this age. More rapid artery calcification was induced by treatment with warfarin together with high doses of vitamin D, a procedure that causes extensive artery calcification by 84 hours. Alendronate and ibandronate again completely inhibited calcification of all arteries and heart valves examined. The subcutaneous doses of alendronate and ibandronate necessary to inhibit artery calcification are comparable to the daily subcutaneous doses of these drugs that have previously been shown to inhibit bone resorption in rats of the same age, with 50% inhibition of artery calcification at 20 microg alendronate x kg(-1) x d(-1) and at 1 microg ibandronate x kg(-1) x d(-1) x Bisphosphonate treatment did not affect serum calcium and phosphate, and so the inhibition of artery calcification cannot be due to a simple lowering of the serum calcium phosphate ion product. We conclude that bisphosphonates inhibit the calcification of arteries and heart valves at doses comparable to the doses that inhibit bone resorption. These results support the hypothesis that artery calcification is linked to bone resorption. The mechanism of this linkage remains to be established, however, and an alternative explanation for the present results is also considered.

Topics: Alendronate; Animals; Aortic Diseases; Bone Resorption; Calcification, Physiologic; Calcinosis; Diphosphonates; Drug Administration Schedule; Etidronic Acid; Female; Humans; Ibandronic Acid; Male; Muscle, Smooth, Vascular; Osteoporosis; Rats; Rats, Sprague-Dawley; Vitamin D; Warfarin

In summary, our 31-year-old patient with hypogonadotrophic hypogonadism has severe osteoporosis caused by chronic oestrogen deficiency. Her GnRH deficiency can be overcome using ovulation induction therapy. However, if she becomes pregnant there is a small risk of recurrent thromboembolism because of her previous cerebral thrombosis. This risk is hard to quantify but would undoubtedly increase if her mobility were impaired. The metabolic and mechanical alterations of pregnancy may compromise her weakened skeleton and increase the risk of a second major fracture. Her skeletal status precludes the use of standard heparin. Fractionated low molecular weight heparins would be the prophylactic agent of choice, possibly switching to low-dose warfarin for the second trimester. Alternative prophylaxis using low-dose aspirin may be suitable, although this is not proven. The difficulty in this case is that pregnancy and the prophylactic measures designed to protect the patient may prove to be detrimental. The case also highlights the vital role of prepregnancy counselling and interdisciplinary consultation between obstetrician, haematologist and endocrinologist in order to steer the safest course through this therapeutic minefield.

Topics: Adolescent; Bone Density; Female; Heparin, Low-Molecular-Weight; Humans; Osteoporosis; Pregnancy; Pregnancy Complications; Pregnancy Complications, Hematologic; Recurrence; Risk Factors; Thromboembolism; Warfarin

Topics: Female; Fetus; Heparin; Humans; Osteoporosis; Pregnancy; Pregnancy Complications; Warfarin