**4. Discussion**

In the study carried out, lower levels of 25OHvitamin D were observed in obese women regardless of age. When evaluating bone metabolism parameters, a higher bone formation marker was observed in younger non-obese postmenopausal women and a higher bone resorption marker (β-crosslap) in older obese postmenopausal women.

An inverse relationship was found between BMI and vitamin D levels, such that obese women had less circulating vitamin D, especially in 59-year-old women, together with high intact PTH values compared to women who were not obese. This effect may be related to vitamin D, which has an inhibiting influence on PTH [8].

The most likely mechanism may be the dilution of vitamin D (as it is a fat-soluble vitamin) in the large fat deposits, decreasing its concentration in the blood [8]. The basis of this dilution is found in the sequestration of vitamin D by adipose tissue [12]. Other mechanisms may be low sun exposure, poor nutrition, or a decrease in the 25-hydroxylation of vitamin D in the liver, but they can also play a role, along with other factors such as inflammation or insulin resistance. However, there is no evidence that these low levels of vitamin D that occur in people with obesity have consequences for bone tissue, although they may have effects on other organs [9].

In obese postmenopausal women, higher resorption markers and lower bone formation markers were observed compared to non-obese postmenopausal women. Regarding the bone resorption marker (β-crosslap) in non-obese women, lower values were found compared to obese women, although it was only significant in older postmenopausal women. The role of age is very important in this sample since they are patients under 65 years of age and this stratification allows us to properly categorize risk. In fact, according to the NHANES study in its 2011 to 2018 cutoff, from the age of 60, the increase in fat mass and the decrease in lean mass are associated with a loss of bone mineral density [13].

The cause could be that in women who were not obese and who were in an early stage of menopause, the estrogen level had not dropped enough to reduce bone formation, since as Cui et al. demonstrated in their study, the significant decrease in bone mass occurs from 45–49 to 55–59 years of age [14]. This evidence contradicts obesity protects bone tissue [6], although obese people maintain circulating estrogens due to peripheral aromatization of androgens in relation to increased fat mass [10,15]. However, estrogen levels are not the only regulators of bone mass and, in fact, in studies such as the one carried out by Corina et al., the estrogenic action of adipose tissue was not observed to have a significant effect on bone, especially in the case of postmenopausal patients [16]. In addition, the adipose tissue also secretes proinflammatory cytokines that could interfere with the balance between bone resorption and formation [3].

No differences were found in the risk of fracture at five years (with a total of 10.30% in the obese versus 10.50% in the non-obese). Regarding the osteoporotic type, it was 2.6% in obese women versus 1.60% in non-obese women. The reason for not finding differences in the risk of fracture between obese and non-obese women could be that there are already alterations at the metabolic level in the bone tissue but that there is not yet a sufficient degree of disease to increase the risk of fracture in obese women [17].

Along these lines, a meta-analysis of 25 cohorts of women aged 63 years and older showed that osteoporotic fractures are less frequent in obese women, but, however, wrist fractures are more frequent compared to non-obese women. No association was found with respect to the most distal part of the lower extremity, but it is thought that these differences in location are related to the pattern of falls, the mechanical force induced by the fall, and that the low BMI of the controls could have masked the fracture risk associated with obesity [18]. However, Adachi et al. showed that obesity does not protect against osteoporotic fractures and even increases the risk of ankle and femur fractures [19].

On the other hand, it has been seen that the distribution of fat mass may be important for bone health, since in two meta-analyses it was observed that abdominal obesity, related to visceral adiposity, was associated with a higher rate of hip fractures [20,21].

These findings can have some implications for the management of these patients. In the first place, it is important to know all the parameters that may affect bone health to plan a therapeutic approach and prevent this bone loss. It is necessary to know how the supplementation of vitamin D and the consumption of calcium and phosphorus may affect this [5]. On the other hand, this bone turnover environment could be affected by weight loss strategies in patients with obesity, and it could increase bone resorption parameters, as it was shown in a study by our group where significant weight loss was associated with an increase in beta-crosslaps [22].

Regarding the main limitations of the study, having chosen two cohorts of women under 65 years of age with recent menopause interferes with the adequate assessment of the risk of fracture, since the negative influence of the decrease in estrogen has not been sufficient. Another associated limitation could be having chosen a short follow-up time (5 years) since a greater number of fractures could have been found in a longer-term follow-up. Another limitation is the lack of measures of adiposity in these patients with body composition, waist and hip, or diabetes presence or absence in all patients. These points could influence over the bone metabolism, and they can be parameters to measure in other studies. Lastly, not having imaging studies that indicate bone mineral density limits the adequate evaluation of the influence on bone metabolism.

In view of the results, there are several possible lines of research, such as the effect of the circulating estrogens in obese postmenopausal women on bone tissue and their functionality, since there are not many studies that identify this functionality.

Likewise, it would also be interesting to carry out a long-term prospective study on the net detrimental or beneficial effect of obesity on bone mass (using imaging tests) and the adequate categorization of fracture risk. It is necessary for the treatment strategies to prevent this bone loss and the possible fracture risk.
