Smoking and bone metabolism in elderly women

doi:10.1016/S8756-3282(00)00341-0

Bone

Volume 27, Issue 3, September 2000, Pages 429-436

Presented as an abstract at the 21st annual meeting of the American Society for Bone and Mineral Research, St. Louis, MO, USA, 1999.

https://doi.org/10.1016/S8756-3282(00)00341-0 Get rights and content

Abstract

Cigarette smoking has been implicated as a risk factor for osteoporosis. In the present study, the relationship between smoking and bone mineral density, calcitropic hormones, calcium absorption, and biochemical indices related to bone and mineral metabolism was examined at baseline, in subjects recruited for an osteoporotic study. The subjects included 489 elderly women, aged 65–77 years. After exclusions (thiazide users), 54 women constituted the smoking group and 390 women were classified as nonsmokers. The effect of frequency of smoking was also examined in this population (33 light smokers [<1 pack/day] and 21 heavy smokers [>1 pack/day]). Adjusted mean total body bone mineral density was 4% lower (0.968 ± 0.019 vs. 1.009 ± 0.004) and the total hip density was 6% lower (0.778 ± 0.024 vs. 0.826 ± 0.006) in heavy smokers compared with nonsmokers. At the other sites measured (spine, midradius, femoral neck, trochanter, and Ward’s triangle), a similar nonsignificant trend was observed. The adjusted mean calcium absorption corrected for weight was lower (13%) both in light and heavy smokers compared with nonsmokers, and serum 25-hydroxyvitamin D was significantly lower (16%) in heavy smokers than nonsmokers. Serum parathryroid hormone (PTH) was higher in heavy smokers, but was not significantly different from that of nonsmokers. A significant increase in bone remodeling markers, serum osteocalcin (4.35 ± 0.271 vs. 3.79 ± 0.066) and urine N-telopeptide/creatinine (NTx/Cr) ratio (74.5 ± 5.75 vs. 49.8 ± 1.4) was seen in heavy smokers compared with nonsmokers. These results suggest that smoking lowers bone mineral density, and is a result of decreased calcium absorption associated with secondary hyperparathyroidism and increased bone resorption.

Introduction

Osteoporosis, the metabolic bone disease involving loss of bone mass and leading to fractures, is a major public health problem in elderly populations of developed countries. Fractures, particularly of the hip and spine, associated with osteoporosis, impose a great economic burden on society, costing about $14 billion a year in USA alone.47 Environmental factors exert a significant influence on bone loss in older men and women. Cigarette smoking is often cited as a risk factor for osteoporosis and associated fractures.

Studies investigating the relation between cigarette smoking and osteoporosis have reported conflicting results. The association between osteoporosis and smoking was first reported by Daniell.4 Following his initial observation, several reports have been published suggesting a positive association between smoking and osteoporosis in both genders.17, 37, 44 Greater incidence of hip, vertebral, and forearm fractures was reported in men and postmenopausal women who smoked cigarettes.5, 9, 48, 49 Furthermore, a recent meta-analysis concluded that smoking was responsible for one in eight hip fractures.28 The increased risk of fractures due to smoking has been attributed partly to reduction in bone mineral density. Krall and Dawson-Hughes25, 26 reported greater bone loss at the radius, femoral neck, and total body in smokers than in nonsmokers. Hopper and Seeman20 examined the effect of cigarette smoking on bone mineral density in 41 twin pairs discordant for at least 5 pack-years of smoking. They observed that, in 20 of the most discordant pairs, bone density was lower in the greater smoking twin at the lumbar spine, femoral neck, and femoral shaft. The reduction in bone density in smokers is probably due to increased bone loss associated with increased bone resorption. In contrast to these reports, other investigators found no relation between cigarette smoking and osteoporosis or fracture risk in women.16, 21, 23 Thus, the influence of smoking on osteoporosis remains unclear.

The exact mechanism by which smoking exerts its negative effect on bone is not yet fully known. Early menopause,23, 30 lower body weight,5, 21, 31 decreased calcium absorption,25, 26 decreased estradiol levels due to either increased catabolism or possible antiestrogenic effect1, 22, 32, 36 are some of the mechanisms proposed to explain the negative effect of smoking. Furthermore, modified lifestyle factors, such as decreased physical exercise, increased alcohol intake or associated nutritional deficiencies,5 direct toxic effect of tobacco on bone cells,6, 8 and cellular resistance to calcitonin,19 have also been proposed to explain the effect of smoking. In addition, smoking is associated with an increased concentration of reactive oxygen species (ROIs) and reduced levels of vitamins.7 It has been suggested that ROIs may be increased in the bone resorption process.12, 43 Mehlus et al.34 recently reported that dietary intake of vitamin E and vitamin C decreases the risk of hip fracture.

The present study examines the relation between smoking and bone mineral density in postmenopausal elderly women. It also investigates the possible alterations in bone and mineral metabolism, which perhaps could better explain the mechanism of the effect of smoking.

Section snippets

Materials and methods

The study population consisted of a total of 489 women, aged 65–77 years, who entered a multicenter osteoporosis intervention trial (Sites Testing Osteoporosis Prevention/or Intervention, or STOP-IT). The baseline data of this study population were used for analysis. The subjects were recruited through advertisements in the local newspaper or by mass mailing of letters inviting them to participate in the 3 year study. The subjects using estrogens were put on a 6 month washout period before the

Characteristics of study population

A total of 489 subjects were recruited at baseline. Of these, 43 women taking thiazide diuretics were excluded from the analysis. Also, one subject with suspected Paget’s disease and one subject with a doubtful smoking status were excluded. Analysis was performed on the remaining 444 subjects.

A comparison of the characteristics among nonsmokers and smokers and by the frequency of smoking (light smokers and heavy smokers) is given in Table 1. Twelve percent of the study population were current

Discussion

The results presented in this report demonstrate that smoking decreases bone mineral density (controlled for confounding variables) in elderly postmenopausal women, and provides further evidence supporting the association between smoking and osteoporosis. In the present study, smoking >1 pack/day was found to significantly affect bone loss, whereas smoking <1 pack/day did not show a significant deleterious effect. Decreased bone mineral density upon smoking was observed at all sites measured

Acknowledgements

This work was supported by National Institutes of Health research grants (Nos. UO1-AG10373 and RO1-AG10358).

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Original articleSmoking and bone metabolism in elderly women

Abstract

Introduction

Section snippets

Materials and methods

Characteristics of study population

Discussion

Acknowledgements

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Clin Nutr

Bone

Lancet

Lancet

Factors associated with appendicular bone mass in older women. The Study of Osteoporotic Fractures Research Group

Ann Intern Med

Osteoporosis and smoking

JAMA

Osteoporosis of the slender smoker. Vertebral compression fractures and loss of metacarpal cortex in relation to postmenopausal cigarette smoking and lack of obesity

Arch Intern Med

Evidence for defective osteoblastic function. A role for alcohol and tobacco consumption in osteoporosis in middle-aged men

Clin Orthop

Interaction between current smoking, leanness, and physical inactivity in the prediction of hip fracture

J Bone Miner Res

Short-term effects of nicotine on bone and calcitropic hormones in adult female rats

Pharmacol Toxicol

Intestinal calcium absorption and serum vitamin D metabolites in normal subjects and osteoporotic patientsEffect of age and dietary calcium

J Clin Invest

Oxygen-derived free radicals stimulate osteoclastic bone resorption in rodent bone in vitro and in vivo

J Clin Invest

Increased bone turnover during gonadotropin-releasing hormone superagonist-induced ovulation inhibition

J Clin Endocrinol Metab

Competitive protein-binding radioassay for 25-hydroxycholecalciferol

J Clin Endocrinol Metab

Assessment of age and risk factors on bone density and bone turnover in healthy premenopausal women

Osteopor Int

Cigarette smoking and bone mineral density in older men and women

Am J Publ Health

Assay of circulating 1,25-dihydroxyvitamin D involving a novel single-cartridge extraction and purification procedure

Clin Chem

Influence of heavy smoking upon the bone mineral content of the radius of the aged and effect of tobacco smoke on the sensitivity to calcitonin of rats

Aktuelle-Gerontol

The bone density of female twins discordant for tobacco use

N Engl J Med

Osteoporosis of the slender smoker revisited by epidemiologic approach

Eur J Clin Invest

Cigarette smoking, serum estrogens, and bone loss during hormone-replacement therapy early after menopause

N Engl J Med

The effect of smoking at different life stages on bone mineral density in elderly men and women

Osteopor Int

Smoking and bone loss among postmenopausal women

J Bone Miner Res

Original article
Smoking and bone metabolism in elderly women