Claim: Certain diabetes drugs found to double bone fracture risk in women
Verdict: SUPPORTS

Retrieved passages:
title: Rosiglitazone
text: with those given metformin or glyburide. The information was based on data from the ADOPT trial The same increase has been found with pioglitazone (Actos), another thiazolidinedione. A meta-analysis of 10 RCTs, involving 13,715 patients and including both rosiglitazone- and pioglitazone-treated patients, showed an overall 45% increased risk of fracture with thiazolidone use compared with placebo or active comparator. It doubled the risk of fractures among women with type 2 diabetes, without a significant increase in risk of fractures among men with type 2 diabetes. The risk of hypoglycaemia is reduced with thiazolidinediones when compared with sulfonylureas; the risk is

title: Osteoporosis
text: fractures, does not affect the risk of nonvertebral fracture. And while it reduces the risk of breast cancer, it increases the risk of blood clots and strokes. Denosumab is also effective for preventing osteoporotic fractures but not in males. In hypogonadal men, testosterone has been shown to improve bone quantity and quality, but, as of 2008, no studies evaluated its effect on fracture risk or in men with a normal testosterone levels. Calcitonin while once recommended is no longer due to the associated risk of cancer and questionable effect on fracture risk. Certain medications like alendronate, etidronate, risedronate, raloxifene, and

title: Dual-energy X-ray absorptiometry
text: fragility fracture, use of glucocorticoids, heavy smoking, excess alcohol intake, rheumatoid arthritis, history of parental hip fracture, chronic renal and liver disease, chronic respiratory disease, long-term use of phenobarbital or phenytoin, celiac disease, inflammatory bowel disease, and other risks. The World Health Organization has defined the following categories based on bone density in white women: The WHO committee did not have enough data to create definitions for men or other ethnic groups. Special considerations are involved in the use of DXA to assess bone mass in children. Specifically, comparing the bone mineral density of children to the reference data of

title: Elagolix
text: limited. In women with risk factors for bone loss and osteoporosis, such as a history of low-trauma fracture, assessment of BMD may be considered. Elagolix should not be used in premenopausal women with known osteoporosis. Supplementation with calcium and/or vitamin D during treatment with elagolix has not been studied, but may be beneficial for helping to maintain bone health. Elagolix decreases the amount, intensity, and duration of menstrual bleeding. Amenorrhea, the cessation of menstruation, was observed in 4 to 17% of women with 150 mg once per day and in 7 to 57% of women with 200 mg twice per

title: Arzoxifene
text: and hip mineral density and had no effect on the uterus and endometrium. Lilly announced in August 2009 that preliminary results from a five-year clinical study showed that arzoxifene met its primary endpoints of reduction in vertebral fractures and breast cancer in postmenopausal women. However arzoxifene failed to meet secondary endpoints of reduction in non-vertebral fractures and cardiovascular events and improvements in cognitive function. Based on these results, Lilly announced they are discontinuing further development of the drug and would not seek regulatory approval. A 2015 network meta-analysis found that arzoxifene significantly reduced the risk of breast cancer ( =

title: Women's Health Initiative
text: outcomes. Women in the CaD trial were already participating in the HT trial, the DM trial, or both. In addition to the global exclusion criteria, component-specific exclusion criteria hypercalcemia, renal calculi, corticosteroid use, and calcitriol use. Among the intervention cohort, a small but significant improvement in hip bone density was observed, although a significant reduction in hip fractures was not observed. However, subgroup analysis revealed a possible benefit to older women in terms of a reduced risk of hip fractures, attributable to calcium plus vitamin D supplementation. It was also found that the intervention did not have an effect on

title: Gliflozin
text: diabetic ketoacidosis (DKA). They can also contribute euglycemic DKA (euDKA) because of the renal tubular absorption of ketone bodies. In September 2015 FDA issued a warning related to canagliflozin (Invokana®) and canagliflozin/metformin (Invokamet®) due to decreased bone mineral density and therefore increased risk of bone fractures. Using gliflozins in combination therapy with metformin can lower the risk of hypoglycemia compared to other T2BM such as sulfonylureas and insulin. Increased risk of lower limb amputation is associated with canagliflozin but further data is needed to confirm this risk associated with different gliflozins. Interactions are important for SGLT2 inhibitors because most T2DM

title: Bone
text: called "postmenopausal osteoporosis", but may develop in men and premenopausal women in the presence of particular hormonal disorders and other chronic diseases or as a result of smoking and medications, specifically glucocorticoids. Osteoporosis usually has no symptoms until a fracture occurs. For this reason, DEXA scans are often done in people with one or more risk factors, who have developed osteoporosis and are at risk of fracture. Osteoporosis treatment includes advice to stop smoking, decrease alcohol consumption, exercise regularly, and have a healthy diet. Calcium and trace mineral supplements may also be advised, as may Vitamin D. When medication is

title: Teriparatide
text: 2015 each dose costs between 579 and 967 USD. Teriparatide is the only anabolic (i.e., bone growing) agent indicated for use in postmenopausal women with osteoporosis at a high risk for fracture or with a history of osteoporotic fracture, patients with multiple risk factors for fracture, and for patients who have failed or are intolerant to other available osteoporosis therapy. It has been FDA-approved since 2002. It is effective in growing bone (e.g., 8% increase in bone density in the spine after one year) and reducing the risk of fragility fractures. Osteoporosis medications are generally safe, but some side effects

title: Thiazolidinedione
text: other risk factors for bladder cancer such as cigarette smoking, family history, or exposure to certain forms of chemotherapy. Thiazolidinediones reduce bone mineral density and increase the risk of fractures in women, possibly as a result of biasing the differentiationof bone marrow stromal cells away from osteoblast differentiation and toward adipocyte formation. Thiazolidinedione The thiazolidinediones , abbreviated as TZD, also known as glitazones after the prototypical drug ciglitazone, are a class of heterocyclic compounds consisting of a five-membered CNS ring. The term usually refers to a family of drugs used in the treatment of diabetes mellitus type 2 that were

title: Human skeleton
text: to the age and sex-matched average, as measured by Dual energy X-ray absorptiometry, with the term "established osteoporosis" including the presence of a fragility fracture. Osteoporosis is most common in women after menopause, when it is called "postmenopausal osteoporosis", but may develop in men and premenopausal women in the presence of particular hormonal disorders and other chronic diseases or as a result of smoking and medications, specifically glucocorticoids. Osteoporosis usually has no symptoms until a fracture occurs. For this reason, DEXA scans are often done in people with one or more risk factors, who have developed osteoporosis and be at

title: Hormone replacement therapy
text: density. Hip fracture is a leading cause of morbidity and mortality in older females, and usually does not occur in the setting of osteoporosis. Estrogen is the only medical therapy that has been shown to prevent hip fractures in women that are not osteoporotic, with efficacy superior to bisphosphonates or calcium and vitamin D supplementation. A 2015 meta-analysis found that HRT was associated with an increased risk of ovarian cancer. The authors concluded that if this association is causal, women using HRT have about one additional case of ovarian cancer per 1,000 users. HRT appears to slow down the biological/epigenetic

title: Women's Health Initiative
text: to a low-fat dietary pattern. The CaD trial component was designed to test the hypothesis that women taking a combination of calcium and vitamin D will experience a reduced risk of hip and other fractures, as well as breast and colorectal cancer. Women participating in this intervention were randomly assigned to receive a regimen of 1000 mg calcium in combination with 400 International Units (IU) of vitamin D (n = 18176) or a placebo (n = 18106), and were followed for an average of 7 years, with monitoring for bone density, fractures, and pathologically confirmed cancers as the measures of

title: Denosumab
text: certain medications, and in those with bone metastases. A 2012 meta-analysis found that denosumab was better than placebo, zoledronic acid and pamidronate in reducing the risk of fractures in those with cancer. In those with postmenopausal osteoporosis it decreases the risk of fractures but increases the risk of infection. A 2013 review concluded that it is a reasonable treatment for this condition. A 2017 review did not find benefit in males. The most common side effects are joint and muscle pain in the arms or legs. There is an increased risk of infections such as cellulitis, hypocalcemia (low blood calcium),

title: Primidone
text: response to earlier findings, and/or that this was because it was sunnier in London than in the Northern European countries which had earlier reported this effect. In any case, the use of more than one anticonvulsant has been associated with an increased prevalence of bone disease in institutionalized epilepsy patients versus institutionalized people who did not have epilepsy. Likewise, postmenopausal women taking anticonvulsants have a greater risk of fracture than their drug-naive counterparts. Anticonvulsants affect the bones in many ways. They cause hypophosphatemia, hypocalcemia, low Vitamin D levels, and increased parathyroid hormone. Anticonvulsants also contribute to the increased rate of

title: Elagolix
text: birth control, and should discontinue the medication if they become or wish to become pregnant. Elagolix should not be used in women with osteoporosis because it may increase the risk of further bone loss. Severe hepatic impairment is associated with 7-fold increased exposure to elagolix, which may increase the risk of bone loss. In women with moderate hepatic impairment, which is associated with 3-fold increased exposure to elagolix, the medication at 200 mg twice per day should not be used, while 150 mg once per day should be used for no more than 6 months. OATP1B1 inhibitors are likely to

title: Osteoporosis
text: strontium ranelate can help to prevent osteoporotic fragility fractures in postmenopausal women with osteoporosis. Although people with osteoporosis have increased mortality due to the complications of fracture, the fracture itself is rarely lethal. Hip fractures can lead to decreased mobility and additional risks of numerous complications (such as deep venous thrombosis and/or pulmonary embolism, and pneumonia). The six-month mortality rate for those aged 50 and above following hip fracture was found to be around 13.5%, with a substantial proportion (almost 13%) needing total assistance to mobilize after a hip fracture. Vertebral fractures, while having a smaller impact on mortality, can

title: Osteoporosis
text: USPSTF does not recommend low dose supplementation (less than 1 g of calcium and 400 IU of vitamin D) in postmenopausal women as there does not appear to be a difference in fracture risk. A 2015 review found little data that supplementation of calcium decreases the risk of fractures. While some meta-analyses have found a benefit of vitamin D supplements combined with calcium for fractures, they did not find a benefit of vitamin D supplements (800 IU/day or less) alone. While supplementation does not appear to affect the risk of death, there is an increased risk of myocardial infarctions with

title: Primidone
text: fractures by causing somnolence, ataxia, and tremor which would cause gait disturbance, further increasing the risk of fractures on top of the increase due to seizures and the restrictions on activity placed on epileptic people.Increased fracture rate has also been reported for carbamazepine, valproate and clonazepam. The risk of fractures is higher for people taking enzyme-inducing anticonvulsants than for people taking non-enzyme-inducing anticonvulsants. In addition to all of the above, primidone can cause arthralgia. Granulocytopenia, agranulocytosis, and red-cell hypoplasia and aplasia, and megaloblastic anemia are rarely associated with the use of primidone. Megaloblastic anemia is actually a group of related

title: Women's Health Initiative
text: of previous observational studies. On the other hand, there were indications for an increased risk of stroke. Unopposed estrogen did reduce the risk for osteoporotic fractures and, unlike the estrogen/progestin treatment, showed a decrease in breast cancer risk. As a consequence of the findings, which indicated that the incurred risks of HT outweigh the identified benefits, the study authors recommended that HT not be prescribed for the purpose of chronic disease prevention in postmenopausal women. The hypothesized and observed risks of specific clinical outcomes are summarized in the following table. Of particular interest are the contrasts between several of the