Repurposing oral contraceptives to limit bone loss in anorexics
Use of oral contraceptives (OC) confers some protection against bone loss in patients with anorexia nervosa (AN), a study has found. Areal bone mineral density (aBMD) preservation improves with longer durations of OC use and shorter delays between disease onset and OC initiation, and appears to be most pronounced in patients more severe forms of AN.
“In this study, a cluster of arguments converges to encourage the prescription of contraceptives to limit bone loss in young patients with AN, particularly in those presenting as extremely underweight. However, as contraceptive use does not provide total protection of bone mass, our results should not be taken as an encouragement to clinicians to rely solely on this treatment to protect bone,” researchers said.
“Instead, they should encourage continued vigilance in monitoring these patients for variations in bone mass,” they added.
The study included 99 OC-user AN patients (mean age, 22.4 years), 206 AN patients not using OC (mean age, 20.9 years) and 121 matched controls (mean age, 21.1 years). Patients in the AN cohorts had lower weight, body fat mass, body fat-free soft tissue (FFST) and aBMD at all sites evaluated (p<0.001 for all) compared with controls.
However, within the AN cohort, OC users had markedly higher aBMD values for the whole body (mean, 1.065 vs 1.023 g/cm2; p<0.001) and the lumbar spine (mean, 0.908 vs 0.853 g/cm2; p<0.001), femoral neck (mean, 0.777 vs 0.731 g/cm2; p<0.01), hip (mean, 0.844 vs 0.792 g/cm2; p<0.01), and radius (mean, 0.533 vs 0.520 g/cm2; p<0.05) compared with nonusers. These differences persisted after multiple adjustments. [Fertil Steril 2019;doi:10.1016/j.fertnstert.2019.01.008]
Preservation of aBMD was significantly associated with OC use duration and time of OC initiation, such that aBMD increased with longer durations of use and shorter delays between disease onset and the start of OC. Furthermore, patients with the lowest body mass index showed the best bone tissue responses to OC.
Bone formation markers, such as osteocalcin and procollagen type I N-terminal propeptide, were lower in the two groups of patients with AN than in the control group. Meanwhile, type I-C telopeptide breakdown products, a marker of bone resorption, were normalized in AN patients using OC.
“The favourable effect of contraceptives does not seem to totally offset the effect of AN on bone tissue, however, because patients taking contraceptives systematically showed a lower aBMD than the control participants of similar age,” researchers said, adding that there are several explanations for it.
One is that that the duration of OC use was shorter than the disease duration, suggesting a period when bone tissue was not protected. Another is that the mode of administration may also affect the drug efficacy. Finally, osteopoenia is much more severe in AN patients compared with normal-weight women with hypothalamic amenorrhoea and an equivalent degree of oestrogen deficiency, underscoring the possibility that its genesis in AN is multifactorial.
Researchers reiterated that despite the positive results for OC, clinicians should not fully depend on this treatment to protect bone in AN patients. “[T]he decision to prescribe OC is not without drawbacks. For example, the return of menstrual function that indicates adequate weight restoration is masked by the withdrawal bleeding induced by the contraceptives. Also, OC use may provide a sense of reassurance that patients are protected against osteopenia, which can reduce efforts at weight rehabilitation.”
Clinicians should consider treatments targeting the increase in bone formation activity, they added. This might include nutritional supplementation (ie, proteins) or mechanical approaches (ie, physical activity), possibly combined with drugs such as recombinant human IGF-I to fully preserve bone tissue in a period of intense bone mass acquisition.