The prevalence of LCPD is highly variable in different populations. Since it is a rare disease, there are very few reports in Mexico and Latin America that describe it. Children with LCPD begin with pain in one or both legs and a slight limp, usually attributed to falls or poor posture. The pain sometimes goes away temporarily, but the lameness continues. Thus, a long journey of visits to various medical services begins, and it usually does not end with a specific diagnosis nor adequate treatment. The correct diagnosis is only given when patients finally go to specialized pediatric orthopedic institutions, such as the INR-LGII. Nevertheless, the number of cases reported in recent years in the INR-LGII is still six to eight cases per year, and each year the number decreases, for the lack of information does not allow an early and specific diagnosis.
The approach to the disease is complicated because its etiology is not yet clear. Genes involved in bone remodeling and architecture have been studied. Furthermore, elevated levels of Hcy have been linked to osteonecrosis . For this reason, we decided to explore variants in the COL1A1 gene that have been studied in relation to osteoporosis and fractures [18,19]. However, none of these variants was informative in the studied sample of Mexican patients with LCPD. It has also been suggested that COL2A1, involved in osteonecrosis of the femoral head, is related to skeletal dysplasia due to failure of cartilage development and growth . However, none of these alterations had significant differences between the patients and the controls studied. Additionally, COL2A1 is suggested to be one of the representative causal genes, as Li et al. found a mutation in COL2A1 G1888A in a Chinese family affected by LCPD and osteonecrosis of the femoral head [12,21], and Miyamoto et al. identified a mutation in COL2A1 G3508A in a Japanese family with LCPD. These findings differ from our results since we found no relationship with LCPD .
The PT G20210A mutation increases the risk of thrombosis . López et al. studied 90 children with LCPD, and no patient had a family or personal history of early thrombotic events. However, four children with LCPD (4.4%) were heterozygous for the G20210A polymorphism compared to controls but without any significant association . Vosmaer et al. found an increase in the incidence of LCPD in the presence of the prothrombin mutation when the FVL polymorphism was also present . Our study did not find significant differences that relate this polymorphism, PT rs1799963, with LCPD.
Common alterations in some genes related to Hcy metabolism, such as MTHFR C677T and CBS T833C, have been shown to cause increased plasma homocysteine levels, thus bringing about a predisposition to thrombosis . Our study did not find these variants, CBS T833C rs5742905, neither in controls nor in patients. Azarpira et al. showed that the MTHFR C677T polymorphism was not associated with the risk of LCPD in Iranian children . When we analyzed the results for the MTHFR C677T rs1801133 polymorphism, it did not present a significant association with the risk of susceptibility to LCPD. However, the frequency of the mutant allele was higher than in the Iranian population, even though several epidemiological case-control studies have found that MTHFR polymorphisms could not play a significant role in the susceptibility to the development of osteonecrosis of the femoral head [28,29]. In this study, we also found that the levels of Hcy between cases and controls present a significant difference (p <0.05). In addition, when adjusting the value of the MTHFR C677T polymorphism whit age, we found a significant association in the recessive model (OR 5.62 (1.02-30.93), p = 0.038).
In general, hyperhomocysteinemia is a risk factor for various diseases: vascular, neurological, diabetes, psoriasis, cancers, including osteoporosis, among others . In addition, Hcy is thought to alter bone remodeling . Furthermore, it has been described that short-term moderate hyperhomocysteinemia affects bone and cartilage characteristics. Trabecular bone microarchitecture is especially sensitive to hyperhomocysteinemia. It shows clearly negative bone balance, mainly due to a decrease in trabecular numbers and markedly reduced trabecular connections, which indicates multiple alterations in collagen due to homocysteine accumulation in bones, indicative of broken collagenous cross-links .