Advancing Early Bone Health: New Frontiers for Osteoporosis Prevention

All factors that influence the peak bone mass achieved at skeletal maturity are important in determining an individual's risk of developing osteoporosis later in life. Bone health begins with maternal health and nutrition, which influence skeletal mass and bone density in utero. The mechanisms underlying the effect of the intrauterine environment on bone health are currently unknown, but certainly include 'fetal programming' of oxidative stress and endocrine systems, as these influence skeletal growth and development later in life.

For the prevention of bone health, the challenges rely 1) in the need for new technology and software specific and applicable to the fetus and newborn; 2) in establishing the effect of environmental contaminants, in particular endocrine disruptors, oxidative stress and subsequent epigenetic changes in mothers and subsequently on the fetus, newborn and infant.

Maximising bone mass during skeletal growth has become the goal of primary prevention of osteopenia and osteoporosis. Any factor that might influence the peak bone mass attained during skeletal maturation is important in determining an individual's risk of developing osteoporosis later in life. Bone health begins with maternal health and nutrition, which influence skeletal mass and bone density in the foetus. The acquisition of peak bone mass is also genetically influenced by both parents. To date, there is some evidence that the risk of osteoporosis in later life may be determined by environmental exposures during intrauterine or early postnatal life. The mechanisms underlying the long-term effects of the intrauterine environment on bone health are currently unknown, but certainly include "fetal programming" of oxidative stress and endocrine systems that influence skeletal growth and development in utero and after birth.

Osteopenia is increasingly diagnosed in low birth weight infants. Intrauterine growth restriction (IUGR) further increases the risk of obesity and metabolic syndrome, conditions that significantly compromise bone quality. Recent studies have highlighted the central role of microRNAs (miRNAs) in bone growth and mineralisation, alongside peptides such as irisin and HMGB-1. These peptides are involved in glucose metabolism and the regulation of adipose and muscle tissue and have recently been linked to bone metabolism. MicroRNAs and long non-coding RNAs (lncRNAs) have gained attention for their ability to regulate gene expression post-transcriptionally, providing epigenetic modifications that influence growth plate and bone development. It remains unclear how maternal nutritional factors affect fetal bone mineral density (BMD) or how variations in fetal BMD may influence birth outcomes, such as spontaneous clavicle or skull fractures during operative delivery, and long-term bone mineralisation.

These findings highlight the importance of assessing skeletal status during the perinatal period. Early identification of conditions that affect bone mass or mineralisation and ongoing monitoring of bone development are essential to improve outcomes.

Radiofrequency echographic multi-spectrometry (REMS) technology has demonstrated its utility in the assessment of BMD in pregnant women. While few studies have investigated the use of transmission ultrasound to assess bone status in neonates, REMS technology shows great promise. Its advantages include the absence of ionising radiation, ease of use and, most importantly, the potential to conduct longitudinal studies of REMS patterns from the intrauterine period into the first year of life.

This innovative approach offers new opportunities to understand the maternal-fetal factors that influence bone health and to develop strategies to optimise bone development from the earliest stages of life.

The aims of the present study are A) To determine the feasibility of using REMS as a precise and innovative technology to assess the skeletal status of fetuses, neonates and children.

B) To assess how maternal REMS patterns and her anthropometric and gestational data influence REMS parameters in the fetus, newborn and during the first year of life.

C) To elucidate the relationships between early exposure to endocrine disrupters, oxidative stress and maternal diet as part of the in utero exposome and later body composition and bone health.

Eligibility Criteria:
Inclusion Criteria:

* term infants from low-risk pregnancy
* (37-42 weeks gestational age)
* Single pregnancy
* Absence of current or previous maternal diseases that could potentially interfere with bone metabolism (e.g., thyroid, kidney, liver disease)
* Absence of motor disability of the mother
* No previous history of recent, previous bone fractures or traumatic fractures (in the mother)
* No intake of vitamin D or other medications during pregnancy
* Maternal age \>18 years
* No diagnosis of osteopenia or osteoporosis according to the criteria of the Italian Society for Osteoporosis, Mineral Metabolism and Bone Diseases (SIOMMMS)

Exclusion Criteria:

* preterm infants
* Infants hospitalized since birth for special conditions
* infants with metabolic disorders
* infants with genetic syndromes