Sustaining a healthy diet has been consistently considered a major factor for preventing major chronic non-communicable diseases (diabetes, hypertension, atherosclerosis, etc.) and mortality (1, 2). Despite this established fact, the most recent Global Nutrition Report (2022) has implicated that among the greatest global public health challenges in modern times are poor or unhealthy diet characterized by over consumption of highly processed foods that are low in nutrients, and malnutrition (3). In fact, a recent large-scale data gathered from 185 countries between 1990 and 2018 demonstrated that while diet quality was considered acceptable for infants and children globally, this pattern appears to worsen over time among older children and adolescents, having relatively lower quality scores compared to adults. This poor-quality score among adolescents needs to be addressed as it can substantially affect their bone health, among others, as it has been established that peak bone mass can be significantly altered by nutrition aside from genetics (4). Dietary calcium and protein in particular impact bone capital, both of which are found in dairy products, and children who consume fewer dairy products are more susceptible to fragility fracture as adults (5). Unfortunately, this poor dietary pattern is most notable in the Middle East and North Africa (MENA) with folate, iron and vitamin D being the most common micronutrient deficiencies (6, 7). Vitamin D deficiency is overwhelmingly common in this region, particularly in Saudi Arabia (SA) where the prevalence remains high, despite abundant year-round sunshine (8). Common factors for vitamin deficiency in SA include extreme heat during summer season, as well as cultural/religious factors such as the full covering of (mostly) women when going outdoors (8). In SA alone, vitamin D deficiency has been linked to a host of extra-skeletal disorders such as cardiovascular disease (9), type 2 diabetes mellitus (10), and premature biological ageing (11). Most of these studies however were conducted in adults, and available data on extra-skeletal effects of vitamin D deficiency in younger Arab populations are scarce.

Among the more well-known effects of chronic, severe vitamin D deficiency in children and adolescents are nutritional rickets and osteomalacia (OM) (12, 13). Their exact prevalence is difficult to ascertain, as they mostly remain clinically underdiagnosed in apparently healthy children and adolescents until symptoms such as hypocalcaemic complications, bone pain, stunted growth and skeletal deformities become apparent (14). The gold standard to confirm a diagnosis of OM is taking a transiliac bone biopsy, which due to its invasive nature is rarely performed. Therefore, non-invasive alternatives such as biochemical markers of OM are gaining more interest lately, despite being an old concept (15). Rickets and OM produce an identical, typical biochemical disease signature (above all elevated levels of parathyroid hormone and alkaline phosphatase). Several operational definitions of biochemical OM have been proposed for epidemiologic studies (15–17). Despite the absence of large-scale studies, nutritional rickets and OM have been reported to be increasing globally, especially among high-risk populations such as dark-skinned individuals and migrant populations (18). To allow early recognition of these hypomineralization disorders, it is therefore essential to establish diagnostic biomarkers.

We have previously investigated the prevalence of biochemical OM, defined as having any 2 of the 4 circulating serum markers of impaired mineralization, namely low 25OH vitamin D (25(OH)D < 30 nmoL/L), elevated alkaline phosphatase (ALP) for age and sex, low calcium (Ca, <2.1 mmoL/L) or low inorganic phosphate (Pi, age and sex-configured values) in a cohort of 2,938 Arab adolescents aged 12–17 years. This study found an over-all prevalence of biochemical OM of 10% (15% in girls and 4% in boys) (19).

Given that 1 in every 10 Arab adolescent in SA has biochemical OM, it is crucial to investigate the influence of diet in the bone health of this understudied population, which, to the best of our knowledge, has never been undertaken on a large-scale. In the present study, we evaluated dietary recall data in the same cohort, to determine the differences in dietary intake of macronutrients, vitamins and trace minerals in Arab adolescents with and without biochemical OM and explore the association of these nutrients with OM based on biomarkers of bone mineralization.

This observational study is part of a large project aimed at establishing the prevalence of biochemical OM among Arab adolescents, which was conducted between September 2019 and March 2021 (19). The study was done in collaboration with the Ministry of Education in SA. Healthy adolescent boys and girls (no acute medical condition or signs and symptoms that required immediate clinical attention, physically and mentally able to engage in school activities) aged 12–17 years enrolled in more than 60 preparatory and secondary schools in Riyadh, SA, were actively recruited to determine the prevalence of biochemical OM (19), and its association with dietary intake of vitamins and minerals in this population (present study). Institutional Review Board (IRB) approval was obtained from the College of Medicine, King Saud University, KSU, Riyadh, SA (E-21-6,095, approved 18 January 2019; amended 7 April 2022). Only adolescents who provided consent/assent, blood samples and dietary recall information were included. Participants were excluded if they did not consent and/or were medically unfit (with physical and/or mental diseases/disabilities that can interfere with blood and data collection) to participate. Expatriate (non-Saudi) adolescents were excluded by default as they were mostly enrolled in community/private schools not covered by the government.

Out of the original 2,938 adolescents who provided blood samples, only 62% or N = 1819 completed the 24 h dietary recall questionnaires. Hence, a total of 1819 (1,083 girls and 736 boys) were included in the present observational study (Figure 1), of whom 175 (9.6%) had biochemical OM (13.5% in girls, 3.9% in boys, p < 0.01). None of the participants had sufficient 25(OH)D level (above or equal to 50 nmoL/L).

The transition of dietary behavior from children to adolescents coincides with a period of more, but not full independence in decision making. It is a crucial period when food preferences are largely influenced by peers and advertisements on various platforms, and less by what is served at home (29). The present study aimed to determine the influence of dietary intakes on circulating biomarkers of hypomineralization among Arab adolescents and found a substantial nutrient imbalance in this population, most notably the very high consumption of foods rich in dietary Pi, Na, K, and Fe exceeding the RDI, with a concomitant very low intake of dietary Ca and vitamin D. We were able to demonstrate that the combination of low dietary Ca and low vitamin D status is associated with the biochemical OM signature. Furthermore, the significant associations of vitamin D status to most dietary intakes including dietary vitamin D were only apparent in the biochemical OM group, while the significant associations of serum ALP and Pi with dietary intakes elicited in all participants modestly varied but remained persistent even after stratification according to biochemical OM status.

The suboptimal nutrient intake of adolescents in the present study, that is, failing to meet the dietary recommendations, is similar to that reported in adolescent populations in industrialized or developing nations (30, 31). The abnormally high median levels of dietary Na, K, and Pi reflect the increased consumption of processed and frozen foods, junk foods and carbonated beverages, to name a few. These foods are known to contain these trace minerals in large amounts, particularly Pi derivatives which are abundant in fast foods (32). This is in sharp contrast with the very low intakes of dietary Ca and vitamin D independent of biochemical OM status. Dietary Ca in particular is significantly lower in boys than girls. Lower intakes of Ca and vitamin D have been more recently documented in a cohort of 631 Saudi adolescents aged 11–18 years (33). Excessive media use, which promotes sedentary lifestyle and negatively affects food choices is particularly common among Saudi adolescents (33), and aggravates this situation. Furthermore, the high consumption of phosphate-derivative foods such as processed foods and beverages confirm a previous survey among almost 11,000 Saudis especially in the young population (34). Interestingly, the low dietary Ca intake in Saudi adolescents extends to their adult counterparts already at risk of osteoporosis, with an average Ca intake of only 445 mg/day (RDI of 1,300 mg/day) (35).

It is worth noting that the influence of dietary intake on markers of bone mineralization appears to be more pronounced among adolescents with biochemical OM, suggesting a compensatory mechanism. Among participants with biochemical OM for instance, protein and thiamine intake were significant predictors of 25(OH)D variation. Fortunately, protein intake of participants was well above the RDI and well within limits for thiamine, suggesting that Arab adolescents consume large amounts of animal-based food in their diet which is compatible with the traditional Saudi diet. Due to the desert environment, vegetables and fruits are infrequently consumed within the region as a whole (36), and apart from dates, the population relies mainly on meat and carbohydrates as their main diet. Aggravated by the country’s current Westernisation, this unbalanced diet has progressively deteriorated to include high amounts of carbonated drinks (such as soda) and processed foods which, as mentioned, are high in Pi content (37). Despite the well-known inverse association between Ca and Pi in bone health (high Pi intake may decrease Ca absorption and high Ca may inhibit Pi uptake in the gut) (38), the elevated dietary Pi intake in our cohort did not protect from developing biochemical OM as the Ca-P product remained low in the OM group independent of Pi intake, indicating that association alone does not imply causation. The significant association of dietary vitamin D intake with serum 25(OH)D among only those without biochemical OM is worth noting since this association, while significant, was very small (r² < 1%) in terms of affecting the participants’ vitamin D status, suggesting that other major factors (i.e., sun exposure, outdoor physical activity, vitamin D supplements) not assessed in the present study are largely influencing the vitamin D status of this population.

ALP was noted to be significantly and inversely associated with most macronutrients as well as dietary mineral intake in the present study, which can probably explain why in our previous study, elevated ALP was also the least common among the 4 markers of impaired mineralization (19). Although ALP isoenzymes were not measured in the present study, it has been observed in animal studies that high protein diet as well as high fat diet with vitamin D restriction can reduce ALP activity (39, 40). The elicited inverse associations of all dietary intake parameters with ALP observed in the present study should be interpreted with caution however, since ALP levels are expected to be high in adolescents, particularly boys, secondary to pubertal bone growth development (41).

Lastly, thiamine and protein were found to be predictors of 25(OH)D in the OM group in the present study, which, at 4% variance, is modest but still statistically significant. Since thiamine is not conventionally known to affect vitamin D metabolism, this association can be explained by the unhealthy dietary choices of participants. A similar study done among Brazilian adolescents aged 10–19 years found that processed and ultra-processed foods was associated with adequate intake of thiamine and inadequate intake of vitamin D and calcium, among others (42), demonstrating a comparable inverse association between thiamine and vitamin D. On the other hand, the significant association of protein intake to 25(OH)D cannot be fully explained and may require additional investigation detailing specific types of meats that held higher levels of vitamin D. Nevertheless, both protein and vitamin D intake are integral in musculoskeletal health, with the latter being a significant contributor in maintaining muscle mass and the former as an anabolic stimuli for muscle protein synthesis (5, 6).

The authors acknowledge several limitations. While the objectives were focused on differences and associations of dietary intake with biochemical OM and markers of impaired mineralization, other factors such as obesity, sunlight exposure and supplement intake were not considered, which could have a profound effect on these markers, 25(OH)D in particular since no observed differences were seen in the dietary vitamin D intake of both groups (43). Supplement intake in this age group however is low especially in females (44). Participants were recruited uniformly during summer time, which from previous observations translate to higher prevalence of vitamin D deficiency as compared to winter season in SA due to sun avoidance behaviour (45). Serum PTH was not assessed since prerequisites for analysis were not met. Hence, the association of PTH with dietary intake in this population was not captured. The operational diagnosis used for biochemical OM is only suggestive and not definitive, since histologic analysis for confirmation was not done. Lastly, the inherent memory recall bias in collecting dietary data, despite being performed by a dietitian, is a limitation. Nevertheless, the study is one of the largest of its kind to confirm whether the recent worsening dietary pattern in terms of quality, as observed among adolescents in the Middle East and SA in particular, is associated with biochemical OM. The findings emphasize the imperative need for food fortification with vitamin D and Ca to optimise nutrition in this vulnerable population who largely fail to meet the RDI (46–49). Additionally, the current national and regional guidelines for vitamin D supplementation are limited to the general adult population (50, 51). We recommend including the youngest and most vulnerable group of children and adolescents into these public health guidelines, in analogy to similar calls for political action worldwide (52, 53).

In conclusion, there is an alarming imbalance in the dietary intake of Saudi adolescents, with very low intakes of dietary Ca and vitamin D and high intakes of dietary Pi together with Na, K, and Fe. This imbalance modestly but significantly affects circulating markers of bone mineralization, contributing to the high prevalence of biochemical OM in Saudi adolescents, particularly girls. Food fortification of essential nutrients such as vitamin D and Ca may help reverse this nutrient disparity since supplementation alone has varying degrees of success.

The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding authors.

The studies involving human participants were reviewed and approved by Institutional Review Board (IRB) approval was obtained from the College of Medicine, King Saud University, KSU, Riyadh, SA (E-21-6,095, approved 18 January 2019; amended 7 April 2022). Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.

NA, SU, and WH: conceptualization, critical revision, and data interpretation. SS: manuscript preparation. NA-D and SY: data collection. KW, SY, and NA-D: data analysis. SH: statistical analysis. All authors contributed to the article and approved the submitted version.

This project was funded by the National Plan for Science, Technology, and Innovation (MAARIFAH), the King Abdulaziz City for Science and Technology, Kingdom of Saudi Arabia (award No. 2-17-03-001-0012).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

The Supplementary material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fnut.2023.1206711/full#supplementary-material