Abstract
Summary
Fractures are increased among prostate cancer patients. No data have been reported in patients with prostate cancer about the relation between serum sex hormone-binding globulin (SHBG) and bone metabolism. We found that SHBG levels were inversely related to bone mass and vertebral fractures in this population.
Introduction
Fractures are increased among prostate cancer patients, especially those on androgen deprivation therapy (ADT), but few data are available on the role of SHBG in their bone status. Our objective was to analyze the relation between serum SHBG and bone metabolism in prostate cancer patients.
Methods
This is a cross-sectional study including 91 subjects with prostate cancer (54 % with ADT). We measured serum levels of SHBG and sex steroids, bone mineral density (BMD) by dual-energy X-ray absorptiometry, and prevalent radiographic vertebral fractures.
Results
SHBG levels were inversely related to BMD (femoral neck: r = −0.299, p = 0.00; total hip: r = −0.259, p = 0.019). Subjects with osteoporosis had higher SHBG concentrations than patients without osteoporosis (60.97 ± 39.56 vs 44.45 ± 23.32 nmol/l, p = 0.022). Patients with SHBG levels in the first quartile (>57.6 nmol/l) had an odds ratio (OR) for osteoporosis of 2.59 (95 % CI, 1.30–5.12; p = 0.009) compared with patients with lower SHBG levels. In patients with SHBG >57.6 nmol/l, the OR for vertebral fractures was 2.34 (95 % CI, 1.15–4.78; p = 0.034). The calculated OR was higher after adjustment for age (OR, 5.16; 95 % CI, 1.09–24.49; p = 0.039), estrogens (OR, 6.45; 95 % CI, 1.44–28.95; p = 0.023), and androgens (OR, 5.51; 95 % CI, 1.36–22.37; p = 0.017).
Conclusions
In prostate cancer patients, SHBG levels were inversely related to bone mass and vertebral fractures. Determination of the serum SHBG level may constitute a useful and straightforward marker for predicting the severity of osteoporosis in these patients.
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References
Heymann JJ, Benson MC, O'Toole KM, Malyszko B, Brody R, Vecchio D, Schiff PB, Mansukhani MM, Ennis RD (2007) Phase II study of neoadjuvant androgen deprivation followed by external-beam radiotherapy with 9 months of androgen deprivation for intermediate- to high-risk localized prostate cancer. J Clin Oncol 25:77–84
Greenspan SL, Coates P, Sereika SM, Nelson JB, Trump DL, Resnick NM (2005) Bone loss after initiation of androgen deprivation therapy in patients with prostate cancer. J Clin Endocrinol Metab 90:6410–6417
Shahinian VB, Kuo YF, Freeman JL, Goodwin JS (2005) Risk of fracture after androgen deprivation for prostate cancer. N Eng J Med 352:154–164
Legrand E, Hedde C, Gallois Y, Degasne I, De Casson FB, Mathieu E, Basle MF, Chappard D, Audran M (2001) Osteoporosis in men: a potential role for the sex hormone binding globulin. Bone 29:90–95
Barrett-Connor E, Mueller JE, von Muhlen DG, Laughlin GA, Schneider DL, Sartoris DJ (2000) Low levels of estradiol are associated with vertebral fractures in older men, but not women: the Rancho Bernardo Study. J Clin Endocrinol Metab 85:219–223
Mellström D, Vandenput L, Mallmin H, Holmberg AH, Lorentzon M, Odén A, Johansson H, Orwoll ES, Labrie F, Karlsson MK, Ljunggren O, Ohlsson C (2008) Older men with low serum estradiol and high serum SHBG have an increased risk of fractures. J Bone Miner Res 23:1552–1560
LeBlanc ES, Nielson CM, Marshall LM, Lapidus JA, Barret-Connor E, Ensrud KE, Hoffman AR, Laughlin G, Ohlsson C, Orwoll ES (2009) The effects of serum testosterone, estradiol, and sex hormone globulin levels on fracture risk in older men. J Clin Endocrinol Metab 94:3337–3346
Tuck SP, Scane AC, Fraser WD, Diver MJ, Eastell R, Francis RM (2008) Sex steroids and bone turnover markers in men with symptomatic vertebral fractures. Bone 43:999–1005
Hoppe E, Bouvard B, Royer M, Audran M, Legrand E (2010) Sex hormone-binding globulin in osteoporosis. Joint Bone Spine 77:306–312
Araujo AB, Travison TG, Leder BZ, McKinlay JB (2008) Correlations between serum testosterone, estradiol, and sex hormone-binding globulin and bone mineral density in a diverse sample of men. J Clin Endocrinol Metab 93:2135–2141
Vermeulen A, Verdonck L, Kaufman JM (1999) A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 84:3666–3672
Sodergard R, Backstrom T, Shanbhang V, Carstensen H (1982) Calculation of free and bound fractions of testosterone and estradiol-17 beta to human plasma proteins at body temperature. J Esteroid Biochem 16:801–810
Landis JR, Koch GG (1977) The measurement of observer agreement for categorical data. Biometrics 33:159–174
Bjørnerem A, Emaus N, Berntsen GKR, Joakimsen RM, Fønnebø V, Wilsgaard T, Øian P, Seeman E, Straume B (2007) Circulating sex steroids, sex hormone-binding globulin, and longitudinal changes in forearm bone mineral density in postmenopausal women and men: the Tromsø study. Calcif Tissue Int 81:65–72
Paller JC, Shields MS, Rohrmann S, Basaria S, Rifai N, Nelson W, Platz EA, Dobs A (2009) Relationship of sex steroid hormones with bone mineral density (BMD) in a nationally representative sample of men. Clin Endocrinol 70:26–34
Smith MR, McGovern FJ, Fallon MA, Schoenfeld D, Kantoff PW, Finkelstein JS (2001) Low bone mineral density in hormone-naïve men with prostate carcinoma. Cancer 91:2238–2245
Rosner W, Hryb DJ, Kahn SM, Nakhla AM, Romas NA (2010) Interactions of sex hormone-binding globulin with target cells. Mol Cell Endocrinol 316:79–85
Hoppé E, Bouvard B, Royer M, Audran M, Legrand E (2010) Sex hormone-binding globulin in osteoporosis. Joint Bone Spine 77:306–312
Fortunati N, Becchis M, Catalano MG, Comba A, Ferrera P, Raineri M, Berta L, Frairia R (1999) Sex hormone-binding globulin, its membrane receptor, and breast cancer: a new approach to the modulation of estradiol action in neoplastic cells. J Steroid Biochem Mol Biol 69:473–479
Fortunati N, Catalano MG (2006) Sex hormone-binding globulin (SHBG) and estradiol cross-talk in breast cancer cells. Horm Metab Res 38:236–240
Orwoll E, Lambert LC, Marshall LM, Phipps K, Blank J, Barret-Connor E, Cauley J, Ensrud K, Cummings S (2006) Testosterone and estradiol among older men. J Clin Endocrinol Metab 91:1336–1344
Center JR, Nguyen TV, Sambrook PN, Eisman JA (2000) Hormonal and biochemical parameters and osteoporotic fractures in elderly men. J Bone Miner Res 15:1405–1411
Mittan D, Lee S, Miller E, Perez RC, Basler JW, Bruder J (2002) Bone loss following hypogonadism in men with prostate cancer treated with GnRH analogs. J Clin Endocrinol Metab 87:3656–3661
Cauley JA, Ewing SK, Taylor BC, Fink HA, Ensrud KE, Bauer DC, Barrett-Connor E, Marshall L, Orwoll ES, Osteoporotic Fractures in Men Study (MrOS) Research Group (2010) Sex steroid hormones in older men: longitudinal associations with 4.5-year change in hip bone mineral density—the osteoporotic fractures in men study. J Clin Endocrinol Metab 95:4314–4323
Wang C, Catlin DH, Demers LM, Starcevic B, Swerdloff RS (2004) Measurement of total serum testosterone in adult men: comparison of current laboratory methods versus liquid chromatography–mass spectrometry. J Clin Endocrinol Metab 89:534–543
Acknowledgments
This work was supported, in part, by RETICEF (RD06/0013/1014) Grants.
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Varsavsky, M., Reyes-García, R., García-Martín, A. et al. SHBG levels are associated with bone loss and vertebral fractures in patients with prostate cancer. Osteoporos Int 24, 713–719 (2013). https://doi.org/10.1007/s00198-012-2012-z
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DOI: https://doi.org/10.1007/s00198-012-2012-z