Effects of Estrogen Plus Progestin on Risk of Fracture and Bone Mineral Density&lt;SUBTITLE&gt;The Women's Health Initiative Randomized Trial&lt;/SUBTITLE&gt;

Cauley, Jane A.; Robbins, John A.; Chen, Zhao; Cummings, Steven R.; Jackson, Rebecca D.; LaCroix, Andrea Z.; LeBoff, Meryl S.; Lewis, Cora E.; McGowan, Joan A.; Neuner, Joan; Pettinger, Mary; Stefanick, Marcia L.; Wactawski‐Wende, Jean; Watts, Nelson B.

doi:10.1001/jama.290.13.1729

Cited by 1,048 publications

(549 citation statements)

References 43 publications

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“…The multivariable-and BMD-adjusted risk of a major OP fracture was 2.3-to 2.5-fold higher in women who had reported a prior low-trauma fracture after the age of 45 years compared with women without a prior fracture history. In agreement with previous studies, (21) we also found that use of postmenopausal HRT resulted in a significant protection against fractures: Current HRT users had a 50% to 60% reduced risk of major OP fractures compared with never users. These results are consistent with those reported in Huopio's study, (15) which to our knowledge is one of the few that concerned a large population of 3000 perimenopausal women who had been followed over 3.6 years and whose mean age at baseline (53 years) was very similar to that in our study.…”

Section: Discussionsupporting

confidence: 93%

Fracture risk prediction using BMD and clinical risk factors in early postmenopausal women: Sensitivity of the WHO FRAX tool

Trémollières

Pouillès

Drewniak

et al. 2010

Journal of Bone and Mineral Research

177

110

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The aim of this prospective study was (1) to identify significant and independent clinical risk factors (CRFs) for major osteoporotic (OP) fracture among peri-and early postmenopausal women, (2) to assess, in this population, the discriminatory capacity of FRAX and bone mineral density (BMD) for the identification of women at high risk of fracture, and (3) to assess whether adding risk factors to either FRAX or BMD would improve discriminatory capacity. The study population included 2651 peri-and early postmenopausal women [mean age (AE SD): 54 AE 4 years] with a mean follow-up period of 13.4 years (AE1.4 years). At baseline, a large set of CRFs was recorded, and vertebral BMD was measured (Lunar, DPX) in all women. Femoral neck BMD also was measured in 1399 women in addition to spine BMD. Women with current or past OP treatment for more than 3 months at baseline (n ¼ 454) were excluded from the analyses. Over the follow-up period, 415 women sustained a first low-energy fracture, including 145 major OP fractures (108 wrist, 44 spine, 20 proximal humerus, and 13 hip). In Cox multivariate regression models, only 3 CRFs were significant predictors of a major OP fracture independent of BMD and age: a personal history of fracture, three or more pregnancies, and current postmenopausal hormone therapy. In the subsample of women who had a hip BMD measurement and who were not receiving OP therapy (including hormone-replacement therapy) at baseline, mean FRAX value was 3.8% (AE2.4%). The overall discriminative value for fracture, as measured by the area under the Receiver Operating Characteristic (ROC) curve (AUC), was equal to 0.63 [95% confidence interval (CI) 0.56-0.69] and 0.66 (95% CI 0.60-0.73), respectively, for FRAX and hip BMD. Sensitivity of both tools was low (ie, around 50% for 30% of the women classified as the highest risk). Adding parity to the predictive model including FRAX or using a simple risk score based on the best predictive model in our population did not significantly improve the discriminatory capacity over BMD alone. Only a limited number of clinical risk factors were found associated with the risk of major OP fracture in peri-and early postmenopausal women. In this population, the FRAX tool, like other risk scores combining CRFs to either BMD or FRAX, had a poor sensitivity for fracture prediction and did not significantly improve the discriminatory value of hip BMD alone. ß

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Section: Discussionsupporting

confidence: 93%

Fracture risk prediction using BMD and clinical risk factors in early postmenopausal women: Sensitivity of the WHO FRAX tool

Trémollières

Pouillès

Drewniak

et al. 2010

Journal of Bone and Mineral Research

177

110

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“…Most studies looking at the effectiveness of HRT in osteoporosis prevention have been carried out on postmenopausal ambulatory women. [52][53][54] No published studies, to our knowledge, have included women with SCI. As the bone mineral density in women with SCI is already reduced due to their paralysis, 31,37 additional bone loss after menopause could put them at higher fracture risk.…”

Section: Discussionmentioning

confidence: 99%

“…The main reasons for starting HRT were menopausal symptoms in 14 women (28%) and osteoporosis prevention in eight women (16%). The mean age when HRT was started was 48.8 years (range [38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56]. Mean duration of treatment was 10.6 years in the 11 women still on HRT (range 6-15) and 7.2 years in the 11 women no longer on HRT (range 0.5-15).…”

Section: Hrt Usementioning

confidence: 99%

Hormone replacement therapy in women with spinal cord injury – a survey with literature review

et al. 2004

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Study design: Postal questionnaire survey. Objective: To examine the current use of hormone replacement therapy (HRT) in a sample of menopausal women with spinal cord injury (SCI). Setting: National Spinal Injuries Centre (NSIC), Stoke Mandeville Hospital, Aylesbury, UK. Method: A postal questionnaire was sent to 94 women from the NSIC patient database who met the study inclusion criteria (wheelchair dependent, aged 49 years and above, last seen or heard from within the last 3 years).Results: A total of 59 valid questionnaires were analysed. At the time of the survey, 50 women were menopausal and 11 of them were using HRT, six for menopausal symptoms and five for osteoporosis prevention. Another 11 had used HRT, eight for menopausal symptoms and three for osteoporosis prevention, but had discontinued it. The main reasons for stopping HRT were side effects. Of the 28 women who had never been on HRT, 20 had either enquired about it, or had been offered HRT, but decided against it. Of the nine women who were still premenopausal at the time of the survey, four would consider using HRT. Conclusions: Results show that 44% of the menopausal women in our sample have used HRT at some point and 22% still do, mostly for treatment of menopausal symptoms and for osteoporosis prevention. In view of the latest literature findings in able-bodied women, use of HRT for osteoporosis prevention in women with SCI may have to be reconsidered.

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“…Hormone therapy (HT) produces significant increases in BMD (Table 1), (23,24) and reductions in BTMs. (25,26) In the Women's Health Initiative (WHI) study of 16,608 women, at 5.2 years combination HT reduced hip and clinical vertebral fractures by 34% and all fractures by 24%.…”

Section: Hormone Therapymentioning

confidence: 99%

Postmenopausal osteoporosis treatment with antiresorptives: Effects of discontinuation or long-term continuation on bone turnover and fracture risk—a perspective

Boonen¹,

Ferrari²,

Miller³

et al. 2012

Journal of Bone and Mineral Research

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Osteoporosis may be a lifelong condition. Robust data regarding the efficacy and safety of both long-term osteoporosis therapy and therapy discontinuation are therefore important. A paucity of clinical trial data regarding the long-term antifracture efficacy of osteoporosis therapies necessitates the use of surrogate endpoints in discussions surrounding long-term use and/or discontinuation. Long-term treatment (beyond 3-4 years) may produce further increases in bone mineral density (BMD) or BMD stability, depending on the specific treatment and the skeletal site. Bisphosphonates, when discontinued, are associated with a prolonged reduction in bone turnover markers (BTMs), with a very gradual increase to pretreatment levels within 3 to 60 months of treatment cessation, depending on the bisphosphonate used and the prior duration of therapy. In contrast, with nonbisphosphonate antiresorptive agents, such as estrogen and denosumab, BTMs rebound to above pretreatment values within months of discontinuation. The pattern of BTM change is generally mirrored by a more or less rapid decrease in BMD. Although the prolonged effect of some bisphosphonates on BTMs and BMD may contribute to residual benefit on bone strength, it may also raise safety concerns. Adequately powered postdiscontinuation fracture studies and conclusive evidence on maintenance or loss of fracture benefit is lacking for bisphosphonates. Similarly, the effects of rapid reversal of bone turnover upon discontinuation of denosumab on fracture risk remain unknown. Ideally, studies evaluating the effects of long-term treatment and treatment discontinuation should be designed to provide head-to-head ''offset'' data between bisphosphonates and nonbisphosphonate antiresorptive agents. In the absence of this, a clinical recommendation for physicians may be to periodically assess the benefits/risks of continuation versus discontinuation versus alternative management strategies. ß

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Effects of Estrogen Plus Progestin on Risk of Fracture and Bone Mineral Density<SUBTITLE>The Women's Health Initiative Randomized Trial</SUBTITLE>

Cited by 1,048 publications

References 43 publications

Fracture risk prediction using BMD and clinical risk factors in early postmenopausal women: Sensitivity of the WHO FRAX tool

Fracture risk prediction using BMD and clinical risk factors in early postmenopausal women: Sensitivity of the WHO FRAX tool

Hormone replacement therapy in women with spinal cord injury – a survey with literature review

Postmenopausal osteoporosis treatment with antiresorptives: Effects of discontinuation or long-term continuation on bone turnover and fracture risk—a perspective

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