Cl: chlorine; INR: international normalized ratio; K: potassium; Na: sodium.

Given the clinical picture and laboratory findings, a simple cranial computed tomography (CT) scan was performed with no evidence of structural alterations, and an abdominal ultrasound showed increased hepatic echogenicity, suggestive of fatty infiltration, without intrahepatic or extrahepatic biliary tract dilatation. Based on the clinical and biochemical findings, the patient was admitted to the intensive care unit (ICU), and treatment for acute kidney injury due to rhabdomyolysis was started with optimization of blood volume and hydroelectrolyte control. During his stay in the ICU, he continued to have neurological integrity without hemodynamic or respiratory deterioration and with adequate urinary flows. However, he presented intense pain in the shoulder that limited mobility and did not improve despite analgesic escalation, so a thoracic CT scan was performed (Figure 2), which showed a bilateral metaphyseal distal multifragmentary fracture of the humerus with a non-displaced fracture of the right coracoid process and a fracture of the anterosuperior aspect of the right glenoid labrum. A surgical procedure of open reduction and internal fixation with a plate with locking screws was performed.

As part of the patient’s diagnostic protocol and since he did not present direct trauma during the seizure, serum vitamin D 25(OH)D levels of 8 ng/mL (reference range of 30-100 ng/mL) and parathyroid hormone levels of 36.8 pg/mL are documented. Based on the recommendations of the Endocrinology Society, supplementation with vitamin D, 8000 IU per day, was started during hospitalization.

Given the history of frequent alcohol consumption and the biochemical findings: neutrophilia, hyperbilirubin, elevated liver enzymes, AST/ALT ratio >1.5, BT >3 mg/dL, and prolonged coagulation times, he was considered at risk of alcoholic liver disease, according to the criteria of the 2018 European Association for the Study of the Liver (EASL), and initiated conservative management and close monitoring of liver function.

Figure 2. Chest three-dimensional computed tomography reconstruction. Bilateral distal metaphyseal multifragmentary fracture of the humerus (white arrow) with non-displaced fracture of the right coracoid process and fracture of the anterosuperior face of the right glenoid labrum. Source: Database, ICU Hospital Juárez de México, 2023.

The patient evolved satisfactorily with correction of renal and hematological function, was asymptomatic, was discharged in good condition after ten days of hospitalization, and subsequently continued with vitamin D at 800 IU per day for three months with serum vitamin D measurements of 28.1 ng/mL. So, it was decided to continue with vitamin D supplementation, physical rehabilitation, and lifestyle changes.

Discussion

The clinical case that we present here shows the relevance that vitamin D has for the organism since it plays an extremely important role in the absorption of calcium at the intestinal level, the maintenance of bones and teeth, as well as the normal functioning of muscles and the immune system.

Vitamin D is a generic term referring to both cholecalciferol (D3) and ergocalciferol (D2). The major circulating form routinely used to assess vitamin D status is 25-hydroxyvitamin (25-OHD), which reliably reflects the free fractions of the vitamin D metabolites. Even though the bioavailable fractions may be more clinically informative(5).

The main function of vitamin D is to maintain a stable extracellular ionic calcium concentration through the stimulation of intestinal calcium absorption and the formation of mature osteoclasts that mobilize calcium from the bone to the extracellular space, which is key to the formation of new bone and correct bone metabolism(6).

Vitamin D maintains an adequate blood phosphocalcium product that generates adequate bone mineralization. This is done through binding to the vitamin D receptor (VDR) on the enterocytes and osteoblasts. Without vitamin D, only 10–15 % of dietary calcium is absorbed, and up to 40.00 % if optimal levels of vitamin D are maintained. A low level of vitamin D stimulates the production of parathyroid hormone (PTH), which releases calcium from the bone, weakening it, to restore the levels of blood phosphocalcium product. This leads to the fact that the levels of 25(OH)D are related to the mineral density, achieving a maximum bone density with levels of 40 ng/ml. From this, it follows that there is a directly proportional relationship between the levels of 25(OH)D reached and the anti-fracture efficacy(7).

The clinical practice guidelines of the Endocrine Society Task Force on Vitamin D have defined a cutoff level of 30 ng/mL as vitamin D deficient. Although there is no consensus on optimal levels of 25(OH)D as measured in serum, vitamin D insufficiency is defined as 21–29 ng/mL, deficiency as less than 20 ng/mL, sufficiency as 30–60 ng/mL, and vitamin D intoxication with levels greater than 150 ng/mL. Levels of 30 ng/mL achieve adequate bone density and good muscle function in the lower extremities, as well as a reduction in the risk of falls, fractures, and colorectal cancer(3,5,7). The most documented factors associated with vitamin D deficiency are: poorer functional capacity, older age, poor sun exposure, lower intake of fatty fish, poorer nutritional status, living alone, and being institutionalized(7).

Specific categories of patients have a very high prevalence of vitamin D deficiency. Patients with chronic renal failure, on hemodialysis, renal transplant recipients, poor nutrition, liver disease, hyperthyroidism, granulomatous diseases, critical illness, and the use of medications such as anticonvulsants, immunosuppressants, and glucocorticoids may have a prevalence of vitamin D deficiency ranging from 85 % to 99 %. In patients with liver failure, there is a severe deficiency characterized by levels <7 ng/mL(5). Available information about the association between alcohol use and vitamin D is still limited. It is suggested that low vitamin D serum levels in chronic alcoholics could be caused by malabsorption due to cholestasis or pancreatic insufficiency, poor dietary intake, lack of sunlight exposure, direct effects on vitamin D metabolism, impaired renal synthesis, and/or increased 1,25(OH)2D degradation, as well as direct bowel mucosal lesions(4).

There is moderate evidence for a positive association of vitamin D with bone mineral density and skeletal fragility. Low vitamin D status is associated with preferential atrophy of type II muscle fibers and influences signaling pathways that regulate inflammation in the skeletal muscle of elderly people at rest and following exercise. Inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), can inhibit muscle protein synthesis and cause greater apoptosis in skeletal muscle. Therefore, vitamin D supplementation can improve muscle function and suppress the synthesis of C-reactive protein, TNF-α, IL-6, and the previously described effects(8). Approximately 85 % of the human skeleton is composed of compact (cortical) bone, demanding a great amount of calcium to mineralize the newly formed bone matrix, which is provided by vitamin D-dependent intestinal calcium absorption(9).

In low-energy fractures with no obvious traumatic mechanism, a higher prevalence has been observed in patients with low levels of vitamin D, especially at the hip level. This is due to secondary hyperparathyroidism that occurs due to the lack of counter-regulation of vitamin D on PTH synthesis, a situation that leads to a considerable increase in bone resorption without adequate replacement of the mineralized matrix, ending in a significant reduction in bone resorption and resistance of this tissue(6).

Stress fractures are the result of excessive stress on the bone due to prolonged and repetitive loading. The association between serum 25(OH)D levels and the occurrence of stress fractures has been previously documented in published studies, especially in military personnel (young and active military recruits). The addition of 2000 mg of calcium and 800 IU of vitamin D demonstrated a 20.00 % reduction in stress fracture incidence, and serum vitamin D levels greater than
40 ng/mL may be considered optimal for preventing stress fractures, especially for active patients with moderate to high functional demand(10,11).

Regarding fractures caused by convulsive crises, there is little updated statistical information; however, some single-center studies report a hospital incidence of 1.1 %, of which 0.50 % presented fracture due to direct trauma, 0.30 % fracture as a consequence of the seizure only, and in 0.30 % the etiology was not documented. These data suggest that fractures secondary to seizures are infrequent, and even more so if they are not associated with trauma(12).

Unless a person eats oily fish frequently, it is very difficult to obtain that much vitamin D3 daily from dietary sources. Sensible sun exposure can provide an adequate amount of vitamin D3, which is stored in body fat and released during the winter, when vitamin D3 cannot be produced. Exposure of arms and legs for 5 to 30 minutes between the hours of 10 a.m. and 3 p.m. twice a week is often adequate. Almost full exposure is equivalent to the ingestion of approximately 20,000 IU of vitamin D2. Excessive exposure to sunlight, especially sunlight that causes sunburn, will increase the risk of skin cancer. Thus, sensible sun exposure and the use of supplements are needed to fulfill the body’s vitamin D requirement(3).

It has been observed that the benefit in preventing fractures is with doses of vitamin D greater than 700–800 IU per day, which becomes relevant when considering that the vast majority of supplements on the market only provide 400 IU, so these doses could not prevent the risk of fractures(6). The reduction in fractures within 6 months of commencing vitamin D supplementation is attributable to the benefits of 1,25(OH)D on muscle function, with a consequent reduction in falls(8).

When a vitamin D deficiency has been diagnosed in the context of a fracture, vitamin D supplementation should be implemented to improve the body’s osseous healing capability. The Endocrine Society has suggested that adults with vitamin D deficiency, regardless of the presence of a fracture, should supplement with 50.000 IU of vitamin D2 or vitamin D3 once a week for 4 to 8 weeks or its equivalent of 6000 IU daily to achieve a 25(OH)D level >30 ng/mL and until fracture healing has occurred. Repeat serum 25(OH)D measurements should be taken every 3 months or after the patient’s treatment course. If adequate levels have been met, the patient should be advised to continue with a lower maintenance supplementation dose of 2000 IU daily to prevent the recurrence of a stress fracture(1,10).

The severity of the deficiency and dose required for treatment will determine the frequency of blood determination for efficacy and safety(1).

Regarding the history of alcoholism, it should be noted that the levels of serum concentration of vitamin D are 28.00 % lower in alcoholics than in non-alcoholics and up to 64 %-92 % in patients with cirrhosis, due to malabsorption caused by cholestasis or pancreatic insufficiency, poor dietary intake, lack of sunlight exposure, impaired renal synthesis, increased 1,25(OH)2D degradation, and direct bowel mucosal lesions. Hypovitaminosis D is an independent risk factor for sarcopenia and osteoporosis in patients with chronic liver disease and, therefore, the risk of fracture(13,14).

Vitamin D deficiency is highly prevalent, but the literature to support vitamin D supplementation is unsatisfactory to date. Unless major funding sources are used for vitamin D research, it appears sensible to focus on vitamin D-deficient populations with a high event rate. Vitamin D is not a panacea but may be an important, inexpensive, and safe adjuvant therapy for many diseases and stages of life, including pregnancy, childhood, and advanced old age. Public health efforts to prevent severe vitamin D deficiency should, therefore, be further promoted.

Vitamin D deficiency is common and often unrecognized, yet it can play an important role in exacerbating underlying pathologies, especially in vulnerable populations and in association with low PTH levels. However, cortical bone loss is associated with bone turnover and vitamin D levels, but not always with PTH levels, as evidenced in this case.

Proximal humeral fractures are common among elderly patients, but not in the young, and less so in the absence of trauma. Most fractures are the result of a fall onto an overextended arm, less frequently from a direct blow. In this case, despite the episode of convulsive crisis, no trauma was documented; however, there was a vitamin D deficiency as a condition for bone fragility.

Regardless of the surgical treatment involved in the fracture, immediate vitamin D supplementation should be performed to improve bone healing capacity and not underestimate the importance of this micronutrient that impacts the osteomuscular level.

Conclusions

This clinical case demonstrates the relevance that vitamin D has for the body, having an important role in the absorption of calcium at the intestinal level as well as in the proper functioning of bones, teeth, muscles, and the immune system. The serious consequences of this fat-soluble vitamin deficiency can lead to pathological fractures at ages where these should not occur, and therefore the doctor must be able to suspect its deficiency for an adequate diagnosis and short- and long-term treatment.

It is important to consider the risk factors for vitamin D deficiency: chronic renal failure, hemodialysis, renal transplant receptors, poor nutrition, liver disease, hyperthyroidism, granulomatous diseases, critical disease, and drugs such as anticonvulsants, immunosuppressives and glucocorticoids.

Vitamin D supplementation improves muscle function and suppresses the synthesis of C-reactive protein, TNF-α, IL-6, and the apoptotic effects that it entails.

The proximal humerus fractures are common among elderly patients, but not in young people, and less in the absence of trauma. In low-energy fractures without obvious traumatic mechanisms, greater prevalence has been observed in patients with low vitamin levels.

For the surgical treatment involved in the fracture, an immediate vitamin D supplementation should be performed to improve the bone healing capacity and not underestimate the importance of this micronutrient that impacts at the osteomuscular level.

Acknowledgments

To the entire team of the intensive care unit of Hospital Juárez de México.

Declaration of authorship

Amezcua-Gutierrez and Medveczky-Ordoñez equally contributed to the conception and design of the research; Amezcua-Gutierrez, Medveczky-Ordoñez, and Garduño-Lopez contributed to the research design; Lopez-Rodriguez and Gasca-Aldama contributed to data acquisition and analysis; Rodriguez-Villanueva, Vidals-Sánchez and Guevara-Cruz contributed to the interpretation of the data; and Amezcua-Gutierrez, Medveczky-Ordoñez, and Garduño-Lopez drafted the manuscript. All authors reviewed the manuscript, agree to be fully responsible for ensuring the completeness and accuracy of the paper, and have read and approved the final manuscript.

Conflict of interest

The authors declare that they have no conflicts of interest.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Ethical disclosures

• Protection of human and animal subjects. The authors declare that no experiments were performed on humans or animals for this study.
• Confidentiality of data. The authors declare that no patient data appears in this article.

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