Fracture Risk Is Decreased in Women With Polycystic Ovary Syndrome: A Register-Based and Population-Based Cohort Study

Abstract

Hyperandrogenism, obesity, and hyperinsulinemia may protect against osteoporosis, whereas amenorrhea, increased cortisol, and low growth hormone may be associated with higher fracture risk in polycystic ovary syndrome (PCOS). The objective of this study was to investigate fracture risk in PCOS. In the PCOS Denmark study, women with PCOS and/or hirsutism were identified in the Danish National Patient Register (1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012). Each patient was assigned three age-matched controls on the index date of PCOS diagnosis. Individuals with a previous endocrine diagnosis were excluded. Within PCOS Denmark, we embedded a wellcharacterized subcohort of patients, PCOS OUH, diagnosed with PCOS at Odense University Hospital (n ¼ 1217). We identified incident fractures by International Classification of Diseases, 10th Revision (ICD-10) codes and used conditional Cox regression analyses to compare fracture risk. In the PCOS Denmark study, there were 19,199 women with PCOS and 57,483 controls were included, mean age 30.6 years (range, 12-60 years). Fracture rates were decreased in PCOS Denmark (10.3/1000 patient years) versus controls (13.6/1000 patient years). The adjusted ORs were 0.76 (95% CI, 0.71 to 0.80) for all fractures, 0.82 (95% CI, 0.74 to 0.92) for major osteoporotic fractures, and 0.57 (95% CI, 0.47 to 0.70) for fractures of head and face. The risk reduction was more pronounced below the age of 30 years at diagnosis. Women with PCOS had significant more hospital contacts due to strains and sprains. In the PCOS OUH subcohort, the risk reduction of fractures did not differ between PCOS women with elevated versus normal testosterone levels and the risk reduction was nominally smaller in overweight versus normal weight PCOS women. Women with PCOS had reduced risk of fractures, in particular of the appendicular skeleton. The risk reduction was greater in women with younger age at diagnosis suggesting that the skeletal effects of PCOS may be greater in women who have not yet reached peak bone mass. Reduced participation in sports activities was probably not the reason for the reduced risk of fractures.

MANAGEMENT OF ENDOCRINE DISEASE: Morbidity in polycystic ovary syndrome

“…One Swedish study found no difference in fracture risk over more than 20 years in 25 postmenopausal women diagnosed previously with PCOS compared with 68 controls (86). In a recent register-based study including 19 199 women with PCOS, we found that the risk of fractures was reduced by about a third in patients with PCOS (82). The risk reduction tended to be more pronounced in women diagnosed with PCOS at a younger age, whereas the presence of hyperandrogenemia did not modify the fracture risk (82).…”

“…In a recent register-based study including 19 199 women with PCOS, we found that the risk of fractures was reduced by about a third in patients with PCOS (82). The risk reduction tended to be more pronounced in women diagnosed with PCOS at a younger age, whereas the presence of hyperandrogenemia did not modify the fracture risk (82). The fracture risk reduction was more pronounced in fractures of the hands, head and face than at major osteoporotic sites and the risk reduction could not be explained by a reduced exposure to daily trauma in PCOS (82).…”

“…Hyperandrogenemia, increased androgen sensitivity, adiposity and hyperinsulinemia in PCOS could be associated with higher bone mineral density and protect against the development of osteoporosis (77,78,79,80,81), whereas amenorrhea, increased risk of T2D, low growth hormone levels and increased cortisol may be associated with lower bone mineral density (82). Furthermore, vitamin D levels were lower in patients with PCOS and hirsutism versus controls (83, 84) and 31-85% patients with PCOS had vitamin D levels <50 nmol/L (85), which could be associated with defects in bone mineralization, increased bone turnover and increased fracture risk (81).…”

“…The mean age of included patients was, however, only 27.1 years and lack of power or limited follow-up period in young individuals could explain that the mortality rate was not increased in PCOS (128,129). Recently, it was reported that patients with PCOS were more often involved in accidents (10) and the prevalence of hospital contacts regarding sprains and strains was increased in PCOS (82). It remains to be established whether a different behavioral risk profile between patients with PCOS and controls could explain these findings.…”

PCOS and bone fractures

“…However, one important issue of the study regards the information of BMI of participants, relevant to speculate about the reasons why PCOS exhibited a higher incidence of bone fractures. This piece of information could help us to understand the contrast of results with a previous population enquire in Denmark which observed a reduction in the number of total fractures in PCOS women before 30 years of age [2]. Indeed, it is not impossible that ethnic variability may also have a role in the occurrence of fractures.…”