Menopause Live - IMS Updates

Date of release: 15 March, 2010

Low bone mass as a predictor for stroke

Anna Nordstrom and colleagues recently investigated prospectively the relationship between bone mineral density (BMD), stroke and death [1]. Previous studies have demonstrated a relationship between osteoporosis and different manifestations of atherosclerosis such as endothelial dysfunction, coronary or carotid atherosclerosis. The aim of the current study was to evaluate BMD and osteoporosis as a prognostic risk factor for stroke and death.


A total of 4302 Swedish men and women (3531 women and 771 men) living in Västerbotten county were evaluated as one group. Their mean age was 54 years (40–75 years), and the mean follow-up time was 5.6 years (0–15.8 years). Femoral BMD was measured using a Lunar densitometer.


As there were no significant differences in BMD between patients suffering hemorrhagic or other types of stroke, all strokes were analyzed together. A total of 93 prospective, validated strokes were registered in women and 46 in men. These 139 subjects were found to be older and having higher body mass index than the 4163 subjects who did not experience stroke (p < 0.05). These 139 subjects were also found to have lower BMD values and a higher prevalence of osteoporosis at the femoral neck (p < 0.05). In a sub-cohort consisting of 1718 men and women including 95 people with strokes, the subjects that sustained a stroke were found to suffer more often from diabetes and were more often treated with antihypertensive drugs or lipid-lowering drugs than the rest of the cohort (p < 0.001). Diastolic blood pressure and physical activity were found to be significantly associated with neck BMD. After adjustment for age, sex and body mass index, every standard deviation decrease in neck BMD and volumetric BMD was associated with an increased hazard ratio (HR) for a stroke of 1.23 (95% confidence interval (CI) 1.01–1.49 for both). After adjustment for the same variables, osteoporosis was found to be an independent prospective risk factor for stroke (HR 1.92, 95% CI 1.11–3.30).


Every standard deviation decrease in neck BMD (HR 1.41, 95% CI 1.21–1.64) and neck volumetric BMD (HR 1.34, 95% CI 1.15–1.55) was found to increase the risk of death. After adjustment for diabetes, current smoking and treatment for hypertension and hyperlipidemia, and physical activity, neck BMD (HR 1.54, 95% CI 1.03–2.29) and osteoporosis (HR 5.30, 95% CI 1.81–15.52) were still associated with the risk of death.


Although osteoporosis, atherosclerosis and stroke are common diseases of old age, they are not usually considered to be related. However, lifestyle factors and certain diseases have previously been demonstrated to be associated with both atherosclerosis and osteoporosis. Although the current study found significant relationships between some of the background variables and BMD, these were rather weak and did not entirely explain the association between low BMD and the risk of stroke or death. In fact, femoral neck BMD was found to be an independent prognostic risk factor for stroke: the diagnosis of osteoporosis almost doubled the future risk for stroke. Furthermore, osteoporosis also increased the risk of death. Other studies have found similar results, measuring BMD of the radius [2] or the calcaneus [3], but, contrary to the previous ones, the present study was homogenic in design, investigating a population from one county.
There are several possible mechanisms for a relationship between osteoporosis and atherosclerotic disease. Genetic studies have revealed certain single nucleotide polymorphisms (SNP) to be associated with both BMD and the risk of atherosclerosis. For example, SNP in the promoter region (G395A) and exon 4 (C1818T) of klotho, which encodes a hormone that represses intracellular signals of insulin and insulin-like growth factor-1, have been associated with both BMD and coronary atherosclerosis [4, 5]. Other proteins of interest include osteoprotegerin, which completely inhibits bone resorption by working as a decoy receptor for receptor activator of NF-ĸB ligand (RANKL), and has also been associated with atherosclerotic manifestations [6], including stroke [7]. Another possible mechanism includes inflammation, which is involved in the pathogenesis of both osteoporosis and atherosclerosis. Since the majority of the Swedish cohort was postmenopausal women, and although the authors did not mention this point, the association between estrogen levels and BMD or risk for atherosclerosis should have been discussed too.


Yair Frenkel
Department of Obstetrics & Gynecology, Sheba Medical Center, Israel


  1. Nordstrom A, Eriksson M, Stegmayer B, Gustafson Y, Nordstrom P. Low bone mineral density is an independent risk factor for stroke and death. Cerebrovascular Dis 2010;29:130-6.

  2. Browner WS, Seeley DG, Vogt TM, Cummings SR. Non-trauma mortality in elderly women with low bone mineral bone density. Study of Osteoporotic Fractures Research Group. Lancet 1991;338:355-8.

  3. Browner WS, Pressman AR, Nevitt MC, Cauley JA, Cummings SR. Association between low bone density and stroke in elderly women. The study of osteoporotic fractures. Stroke 1993;24:940-6.

  4. Kawano K, Ogata N, Chiano M, et al. Klotho gene polymorphisms associated with bone density of aged postmenopausal women. J Bone Miner Res 2002;17:1744-51.

  5. Imamura A, Okumura K, Ogawa Y, et al. Klotho gene polymorphism may be a genetic risk factor for atherosclerotic coronary artery disease but not for vasospastic angina in Japanese. Clin Chim Acta 2006;371:6670.

  6. Jono S, Ikari Y, Shioi A, et al. Serum ostoprotegerin levels are associated with the presence and severity of coronary artery disease. Circulation 2002;106:1192-4.

  7. Strand M, Soderstrom I, Wiklund PG, et al. Polymorphism at the osteoprotegrin and interleukin-6 genes in relation to first-ever stroke. Cerebrovascular Dis 2007;24:418-25.