Review Question - QID 219175

Vitamin D has been shown to have several mechanisms in reference to healing, both wound and fracture, but overall, the results show that the most important effect of Vitamin D is regulation of inflammation.

The role of Vitamin D in the bone healing process continues to be an extensively studied topic. At the molecular level, it has been shown to improve muscle and soft-tissue growth and prevent infection, particularly through its role in the regulation of the inflammatory cascade. Research has shown that macrophages, neutrophils, and T cells all express Vitamin D receptors (VDRs) and are able to locally convert Vitamin D in response to pathogenic stimulation, thereby regulating the cellular response to injury. More specifically, in terms of fracture healing, activities between fibroblasts, chondrocytes, and osteoblasts are critical for soft callus formation via deposition of woven bone and collagen and for fracture closure via mineralization. Following soft callus formation, osteoblast-driven mineralization of woven bone has been shown to be influenced by Vitamin D-mediated stimulation of mesenchymal stem cell (MSC) commitment to osteoblastic lineage through adhesion to matrix proteins and the expression of integrins. Furthermore, at the functional level, Vitamin D has been shown to stimulate the production of collagenous and non-collagenous extraceullar matrix (ECM) proteins including collagen I, osteocalcin, and osteopontin. Taken as a whole, the physiologic effects of Vitamin D are far-reaching and its status and ability of various cells to utilize it are critical to maintaining overall health and promoting optimal healing.

Nino et al. review Vitamin D and metabolic supplementation in orthopedic trauma. The authors note that Vitamin D is a subclass of fat-soluble steroids and is essential to calcium, phosphate, and parathyroid hormone (PTH) homeostasis in the human body. When fracture nonunion occurs without a clear cause, it is reasonable to be suspicious that the patient may have a metabolic or endocrine abnormality, and the role of Vitamin D should be investigated to prevent a costly complication. They conclude with the recommendation that orthopedic surgeons should assume a role in the diagnosis and treatment of patients with potential Vitamin D deficiency given its importance in musculoskeletal homeostasis.

Valerio et al. review the pleiotropic actions of Vitamin D in composite musculoskeletal trauma involving complex and devastating wounds usually caused by high energy impacts such as motor vehicle accidents or within the military context such as blast injuries. The authors specifically identified factors that promote tissue regeneration and mitigate inflammation, one being Vitamin D, as being key to restoring wound healing after composite tissue injury. They note that beyond its traditionally cited roles, the pleiotropic and localized actions of Vitamin D are increasingly being recognized in most aspects of wound healing in complex tissue injuries –e.g., regulation of inflammation, myogenesis, and fracture callus mineralization. They conclude that the Vitamin D deficient state requires acute supplementation in order to quickly restore circulating levels to an optimal level, thereby facilitating a robust wound healing response.

Patton et al. review Vitamin D as an important component in musculoskeletal development, maintenance, and function within the field of orthopaedics. The authors note that the action of Vitamin D at the cellular level requires that it bind to the Vitamin D receptor (VDR), with polymorphisms in the VDR gene having been linked to various musculoskeletal conditions, including low bone mineral density in adolescent idiopathic scoliosis patients, as well as multilevel degenerative disk disease in young adults. The authors conclude by recommending active involvement by the orthopaedic surgeon in the diagnosis and treatment of patients with potential Vitamin D deficiency.

Figure A is a lateral radiograph of the lumbar spine demonstrating an osteoporotic fracture of the L1 vertebra in the setting of prior L1-pelvis fixation.

Incorrect Answers:
Answer 1: While an important factor in osteoblastogenesis, Vitamin D (along with FGF23) has been shown to inhibit the activity of the osteoclast, thus allowing for increased bone mass.
Answer 2: Conversely, Vitamin D has been shown to promote vasculogenesis and invasion into the wound healing bed by regulating VEGF and other growth factors.
Answer 3: Vitamin D supplementation has been shown to have a positive effect on fracture healing by stimulating mesenchymal stem cell (MSC) commitment to osteoblastic lineage through adhesion to matrix proteins and the expression of integrins.
Answer 4: Vitamin D stimulates rather than inhibits the production of collagenous and non-collagenous extracellular matrix (ECM) proteins including collagen I, osteocalcin, and osteopontin.