Orthopedics. Volume 2013, Article ID 471695,12 pages http://dx.doi.org/10.1155/2013/471695
William J. Rodriguez and Jason Gromelski
Nola Physical Therapy, 2 West 45th Street, Suite 208, New York, NY 10036, USA Correspondence should be addressed to William J. Rodriguez; rodrig.bill at gmail.com Received 20 February 2013; Accepted 19 March 2013
- Yes, need to normalize vitamin D levels after spinal surgery
- Need to also normalize vitamin D levels BEFORE spinal surgery – and thus perhaps eliminate the surgery
See also VitaminDWiki
- Give Vitamin D before all spinal surgeries – no testing needed – June 2020
- Search VitaminDWiki for backpain OR "back pain" 79 as of Nov 2013
- Search VitaminDWiki for Musculoskeletal Pain 189 items Aug 2016
- Back pain associated with less than 40 ng vitamin D – March 2013
- Daily headaches and musculoskeletal pain may be due to low vitamin D – Oct 2013
- Overview Pain and Vitamin D
- Back pain reduced for 95 percent of those who took vitamin D - 2003 PDF file
5,000 - 10,000 IU vitamin D3 intervention
- Spinal fusion improved by vitamin D (no amounts stated in abstract) – Jan 2015
- Back Pain
There is a high prevalence of hypovitaminosis D in patients with back pain regardless of whether or not they require surgical intervention. Furthermore, the risk of hypovitaminosis D is not limited to individuals with traditional clinical risk factors. Vitamin D plays an essential role in bone formation, maintenance, and remodeling, as well as muscle function. Published data indicate that hypovitaminosis D could adversely affect bone formation and muscle function in multiple ways. The literature contains numerous reports of myopathy and/or musculoskeletal pain associated with hypovitaminosis D. In terms of spinal fusion outcomes, a patient may have a significant decrease in pain and the presence of denovo bone on an X-ray, yet their functional ability may remain severely limited. Hypovitaminosis D may be a contributing factor to the persistent postoperative pain experienced by these patients. Indeed, hypovitaminosis D is not asymptomatic, and symptoms can manifest themselves independent of the musculoskeletal pathological changes associated with conditions like osteomalacia. It appears that vitamin D status is routinely overlooked, and there is a need to raise awareness about its importance among all healthcare practitioners who treat spine patients.
A large portion of the United States population experiences low back pain, and an increasing number undergo spinal fusion each year. While many patients achieve a satisfactory outcome, there is a subpopulation that fails to achieve acceptable outcomes. These patients may have obvious causes for their outcomes (e.g., pseudarthrosis); however, there are those that are deemed fused yet continue to experience low back pain and other symptoms. Although many factors may be considered when a patient experiences a suboptimal outcome following spinal fusion surgery, serum vitamin D concentration is rarely considered even though most physicians acknowledge its importance in maintaining musculoskeletal health.In this review,we discuss the role of vitamin D in musculoskeletal health especially in relation to low back pain and outcomes of spinal fusion surgery. Our discussion includes the risk factors and prevalence rates of hypovitaminosis D as well as the literature published on vitamin D and spinal surgery. A key concept is the fact that hypovitaminosis D is not asymptomatic, and we delineate the mechanisms by which hypovitaminosis D can adversely affect spinal fusion outcomes.
VitaminD has numerous and varied roles in the body, this is underscored by the fact that the vitamin D receptor (VDR) has been identified in several dozen diverse tissues and cells, including those not involved in calcium homeostasis . Two types of VDRs have been identified, and ligand binding to each type activates a distinct signal transduction pathway. The first type of receptor identified was a nuclear VDR (VDRnuc). The genomic responses that result from the activation of VDRnuc include transcriptional regulation of specific genes [65, 66]. The second type of receptor identified was a cell surface VDR (VDRmem). Activation of the VDRmem results in rapid local responses like the opening of voltage-gated calcium channels and transcaltachia—rapid stimulation of intestinal calcium absorption [67-69]. Studies of VDR knockout mice revealed muscular effects one might not expect like muscle fibers with smaller diameters and postural control abnormalities [70-72]. However, the best-known role of vitamin D is its role in calcium homeostasis; appropriate serum calcium concentrations are essential for many functions, including proper mineralization of the bone, muscle contraction, and transmission of nerve impulses. And studies ofVDR knockout mice also revealed the metabolicand skeletal abnormalities one would expect like secondary hyper-parathyroidism, hypocalcemia, osteomalacia, and growth retardation .
Vitamin D deficiency can result in musculoskeletal pathological changes. The traditional understanding is that vitamin D deficiency eventually results in changes like hypocalcemia and secondary hyperparathyroidism. These changes can lead to the upregulation of osteoclastic activity resulting in resorption of mineral content from bone tissue; prolonged demineralization and the resulting weakening of bone tissue eventually upregulate osteoblastic activity. However, due to the inadequate calcium and phosphate concentrations, the newly formed osteoid is not sufficiently mineralized. Interestingly, recent data indicates that individuals may be vitamin D deficient and have increased bone turnover without having secondary hyperparathyroidism . Previous studies confirmed that hypovitaminosis D increases bone turnover and that individuals may have hypovitaminosis D without secondary hyperparathyroidism [10, 13, 17, 41, 74-76]. Therefore, vitamin D appears to play a direct role in bone formation, maintenance, and remodeling; indeed VDRs have been identified in both osteoblasts and osteoclasts [65, 77-79].
Data reveal that osteoblasts express both nuclear and membrane VDRs . Vitamin D treatment of osteoblasts leads to increased synthesis of bone matrix proteins as well as extracellular signals involved in angiogenesis like vascular endothelial growth factor [65, 80]. Vitamin D also causes a calcium influx into osteoblasts, and this influx is not required for the increased synthesis of bone matrix proteins . Additional data shows that vitamin D-VDR binding in osteoblasts regulates osteoclast formation . There appears to be conflicting data in the literature regarding the role of vitamin D and osteoclasts [78, 82]. However, closer examination of the literature reveals that vitamin D may affect osteoclastic activity in two separate ways. First, the most studied interaction, vitamin D can induce osteoclast formation [81, 82]. This occurs indirectly via vitamin D interaction with osteoblasts, which in turn interact with osteoclast precursor cells. Takeda et al. demonstrated that VDR knockout mice (VDR-null)could form osteoclasts. Osteoclasts were formed when osteoblasts and osteoclast precursors, both VDR-null, were cultured together and treated with either parathyroid hormone (PTH) or IL-1a . However, if osteoblasts and osteoclast precursor cells, both VDR-null, were cultured together and treated with vitamin D, osteo-clasts were not formed . Finally, when VDR-expressing (wild-type) osteoblasts were cultured with VDR-null osteo-clast precursors, osteoclast formation occurred with vitamin D treatment 81]. Taken together these data show that osteoclast formation can be induced by multiple, independent signals (i.e., PTH and vitamin D), and that a VDR expressed by osteoblasts mediates vitamin D-induced formation of osteoclasts. There is a second, less studied role of vitamin D in regards to osteoclastic activity—the direct interaction of vitamin D with osteoclasts [77, 78]. Takasu et al. showed that vitamin D could decrease osteoclast formation and that a VDR expressed by osteoclast precursors mediates this activity . Therefore, it appears that vitamin D may regulate osteoclastic activity via two different mechanisms—indirectly (via osteoblasts) and directly. Osteoclastic activity is often thought of in a negative manner; this, however, is not the case unless it is uncoupled from osteoblastic activity and/or inappropriately high. In fact, osteoclastic activity is a necessary part of healthy bone formation and maintenance.
One thing is certain, whether via an indirect role (involving PTH), a direct role, or both, vitamin D plays an essential role in bone formation and maintenance. In vivo studies on the effect of vitamin D on fracture healing confirm this. Fu et al. investigated the effect of vitamin D on osteoporotic fracture healing in an ovariectomized rat model [ 83]. Delayed healing occurred in the control group compared to the vitamin D-treated group at 6 and 16 weeks after fracture . This was demonstrated in each of several measures: radiographic (X-rays and micro-CT scans), biomechanical testing, and histological examination. At 6 weeks after fracture, the vitamin D-treated group had a greater amount of bony callus compared to the control group; the vitamin D group also had continuous callus and mature woven bone, whereas the control group had delayed endochondral ossification . Biomechanically, at 6 weeks, the ultimate load at failure and energy absorption were 96% and 95% higher in the vitamin D group, respectively . Histological examination at 16 weeks revealed remodeled mature bone at the fracture site in the vitamin D group, whereas the control group was still undergoing endochondral ossification; both biomechanical measures were higher in the vitamin D group at this time point as well . This in vivo study and others demonstrate that vitamin D treatment results in accelerated bone healing and maturation, as well as stronger bone tissue [84, 85]. A randomized placebo-controlled study of proximal humerus fracture healing in women revealed similar results . Unfortunately, the treatment group received both vitamin D and calcium; therefore, one must attribute the results to the combined effect. However, the data is in accordance with vitamin D only treatment in the previously discussed studies. At 6 weeks after fracture, the treatment group had a significantly higher increase in bone mineral density compared to the control group . Finally, hypovitaminosis D-delayed bone formation and healing may account for the findings of Brinker et al. in patients with nonunions .
In summary, published data indicate that hypovitaminosis D could adversely affect bone formation in multiple ways: (1) decreasing intestinal calcium absorption thereby limiting calcium availability for both mineralization of newly formed osteoid and cellular functions; (2) altering both the number and activity of osteoblasts and osteoclasts. Although PTH can play a role in each of these effects, vitamin D can affect both independent of PTH. Therefore, in terms of spinal surgery patients, hypovitaminosis D could result in delayed spinal fusion or pseudarthrosis, as well as impaired osseointegration of implanted spinal hardware.
Both types of VDRs have been identified in human skeletal muscle cells [87-89]. Vitamin D can directly affect skeletal muscle cells in multiple ways. It affects phosphate transport and phospholipid metabolism; in addition, calcium metabolism and transport is affected at both the genomic and nongenomic levels [90-94]. Vitamin D also promotes muscle cell proliferation, growth, and differentiation [72, 95-97]. Studies of myopathy associated with hypovitaminosis D began appearing in the 1960s and have continued to the present 43, 98-101]. This myopathy has been observed in patients with and without osteomalacia as well as with and without hyperparathyroidism[98, 99,102-107]. The myopathy is described as muscular atrophy and weakness [98, 100, 101, 103, 105, 106]. Unfortunately, many review articles restrict their description of the muscle weakness to proximal muscle weakness, they often mention altered gait also. However, Mytton et al. reported that proximal muscle weakness and gait change occurred in less than 3% and 2% of patients with this myopathy, respectively. Others reported findings similar to Mytton et al. [10, 109]. Additionally, patients often complain of fatigue [14, 49, 102, 107, 108]. Vitamin D treatment has been shown to improve these symptoms [98, 100, 102, 107, 110-112].
In terms of clinical studies of vitamin D and muscle function, some apparently conflicting data have been published. There are reviews solely dedicated to vitamin D and skeletal muscle that address this issue . Nevertheless, both in vitro and in vivo studies demonstrate that vitamin D plays a direct role in normal muscular function. In fact, human studies have revealed the effect of vitamin D on muscle fibers. Vitamin D deficient adults have been shown to have type II muscle fiber atrophy, and vitamin D treatment increased both the amount and diameter of type II muscle fibers [110, 114]. Two areas are particularly relevant to the outcomes of spine surgery patients in regards to hypovitaminosis D and impaired muscle function: first, trunk stability because spine patients require core strength and stability, especially during the fusion process ; second, lower limb weakness because many spine patients have lower limb muscle atrophy. Prolonged weakness in these two areas may lead to extended use of assistance devices (e.g., back braces and canes) [99, 105, 106]. Furthermore, protracted core weakness also may place additional stress on implanted hardware and/or adjacent spinal segments.
There are numerous reports of musculoskeletal pain associated with hypovitaminosis D [10,14, 43-45,48, 49,102,103,107-109,116-119]. This pain is described as both bone pain and muscular pain [14, 49,108]. The bone pain is reported as both excluding the joints and including the joints 102,107,109]. Often, but not always, the musculoskeletal pain begins in the lowback [107-109]. Vitamin D treatment has been shown to improve these symptoms [43-45, 48, 102, 107, 109, 117, 120]. Resolution of symptoms often occurs between three and seven months [102,107,109].
The mechanism often proposed to generate hypovitaminosis D-related musculoskeletal pain is that insufficiently mineralized osteoid absorbs fluid and swells; the expanded osteoid then exerts pressure on the periosteum and corresponding nociceptors, thus generating pain [14, 63,119]. However, Tague et al. recently published neurological data which implicates a different mechanism . First, Tague and Smith identified VDRs on sensory neurons . Next, in a separate publication, they demonstrated that vitamin D deficiency produced muscle hypersensitivity and balance deficits in rats similar to those observed in humans . Vitamin D deficiency resulted in nociceptor hyperinnervation and hypersensitivity that was specific to skeletal muscle tissue; neither occurred in rat hindpaw skin . Interestingly, increased calcium intake exacerbated the adverse effects instead of ameliorating them . Their model was one of early vitamin D deficiency and not prolonged deficiency. Therefore, the pathological features of prolonged vitamin D deficiency were not observed, including altered bone morphology and muscle atrophy . From these data, they concluded that it is unlikely that musculoskeletal pain during early vitamin D deficiency is the result of either skeletal or muscle pathology, rather it is the result of an increased density of pain sensing nerves in muscle tissue . However, as previously discussed, musculoskeletal pathology is known to occur with prolonged hypovitaminosis D. It may be that both of these mechanisms (nociceptor hyperinnervation and musculoskeletal pathological changes like expanded osteoid) work either independently or concomitantly to generate pain in patients with hypovitaminosis D. Finally, in terms of clinical relevancy, both animal and human data show that insufficient 25(OH)D concentrations can produce symptoms in patients prior to and/or independent of the pathological changes that are thought of in connection with vitamin D deficiency [10, 102,121]. Therefore, hypovitaminosis D is not asymptomatic.
Unfortunately, there is a dearth of vitamin D-related spine data, and only four articles have data from 30 or more patients [10, 46-48]. The limited number of spine studies include both spinal surgery patients and those without surgical intervention [10, 42-48]. Two studies examined correlations between pain and 25(OH)D concentrations in patients with back pain. The first study reported that patients with chronic backpain had significantly lower 25(OH)D concentrations compared to a control group . The second, a study of preoperative spinal fusion patients, found that those with vitamin D deficiency had greater pain and higher disability scores . The symptoms described for spine patients with hypovitaminosis D are similar to those discussed in the sections on muscle function and musculoskeletal pain [10,42-45,47,48]. Treatment with vitamin D has been shown to improve these symptoms [42-45, 48]. One study reported that 95% of all patients and 100% of patients with severe vitamin D deficiency had resolution of chronic low back pain three months following vitamin D treatment . Similar results have been reported for patients with chronic back pain and failed spinal fusion surgery [42, 44, 45].
Of the two spinal fusion studies with greater than 30 patients, one reported preoperative data only and the other pre- and postoperative data [46,47]. As previously discussed, Stoker et al. reported an association between vitamin D deficiency and pain and disability scores, as well as a high prevalence of hypovitaminosis D in a study of 313 patients . The second article looked at 31 female spinal fusion patients and found all to have hypovitaminosisD preoperatively and 16% to be vitamin D sufficient 1-year postoperatively . Vitamin D treatment was not part of this study, as the premise was that patients' 25(OH)D concentrations would increase postoperatively due to the increased mobility. However, the premise holds true only for those patients whose 25(OH)D concentration is limited by their level of mobility; increased mobility would most likely involve increased UVB exposure. However, as previously discussed, Binkley et al. demonstrated that abundant UVB exposure does not ensure vitamin D sufficiency . Therefore, even if all patients' UVB exposure significantly increased postoperatively, only a portion would achieve sufficient 25(OH)D concentrations. And, the data revealed this, only 16% of patients had sufficient 25(OH)D concentrations after 1 year; the remaining 84% still had hypovitaminosis D and, therefore, were at risk for musculoskeletal symptoms like pain, myopathy, and delayed fusion or pseudarthrosis . A correlation between postoperative 25(OH)D concentration and Oswestry disability index (ODI) scores was observed . Unfortunately, 1-year postoperative fusion status data was not reported.
Even though there is limited spine data, several conclusions can be drawn.
- First, there is a high prevalence of hypovitaminosis D in patients with back pain regardless of whether or not they require surgical intervention.
- Second, spine patients with hypovitaminosis D display symptoms similar to other populations with hypovitaminosis D, and the correlation between pain and 25(OH)D concentration also holds true for spine patients.
- Third, in the absence of an intervention with vitamin D supplementation the majority of spine patients will not achieve sufficient 25(OH)D concentrations after a surgical intervention.
- Finally, patients with hypovitaminosis D may experience delayed fusion or pseudarthrosis and/or a return of persistent pain that requires revision surgery and/or vitamin D treatment [42-45].
Although not spinal fusion studies, two recent articles on THA and vitamin D status should be addressed [7, 8]. These studies looked at functional milestones in-hospital and at 6 weeks postoperatively [7, 8]. Neither study found an association between 25(OH)D concentration and functional outcomes. However, the functional outcomes were bare minimum measures and, therefore, would not likely reveal differences between vitamin D sufficient and insufficient patients. The main item these studies reveal is that there are different perspectives of functional outcomes and surgical success; although a patient may qualify as having a technically successful outcome by certain measures, their actual functional ability may be severely limited.
Often successful spinal fusion surgery is defined by the appearance of de novo bone tissue on plain radiographs. However, using X-rays (whether static or dynamic) to evaluate the status of a fusion site has severe limitations. First, surgical implants make evaluation difficult. Second, bone grafts (both natural and synthetic) can be mistaken for de novo bone formation [123,124]. Spinal fusion studies demonstrate that sites deemed fused via X-rays actually contained large amounts of fibrous tissue when assessed via CT scan and/or histology [123-125]. Therefore, patients may be deemed fused without being fully fused. Additionally, successful spinal fusion surgery maybe defined as a significant decrease in pain and disability scores (e.g., ODI and SF-36). Unfortunately, there is a subpopulation of spinal fusion patients that are considered technically successful in this regard yet are wholly unsuccessful in terms of their residual pain and disability. Although considered a success, these patients require ongoing treatment for their pain and may continue to have extensive limitations on their mobility and ability to sit, perform weight-bearing activities, and/or return to work. We think (based on the data discussed in this review) that hypovitaminosis D may be a major contributing factor to the symptoms experienced by these patients.
Published data reveals that physicians routinely neglect evaluating the vitamin D status of a patient. A study of patients with musculoskeletal pain for at least one year found that although greater than 90% had been medically evaluated for their chronic pain, none had been tested for hypovitaminosis D . Upon testing, the prevalence rate for this group was determined to be 93%; furthermore, five of the patients had undetectable 25(OH)D concentrations . Apparently many spine surgeons regularly overlook vitamin D status and underestimate its importance as well. One survey of orthopedic surgeons and neurosurgeons who treat spine conditions found that metabolic bone laboratories (vitamin D, PTH, and calcium) were utilized by 12% and 20% of spine surgeons as part of a workup for preoperative fusion and pseudarthrosis patients, respectively . Furthermore, 33% of those who do not routinely check metabolic bone laboratory tests stated that, "they did not think it would affect clinical management" . Interestingly, of those surveyed, 71% had completed a spine fellowship, and 32% were affiliated with an academic institution . Publications by those who have utilized vitamin D to treat patients with chronic pain due to failed spine surgery confirm that surgical intervention, pain management, and/or physical rehabilitation often are considered while vitamin D status is an afterthought at best [42-45]. Therefore, there is a need to raise awareness about the importance of vitamin D status among all healthcare practitioners who treat spine patients.
Given the high prevalence of hypovitaminosis D among the general population as well as spine patients and that it is difficult to predict its presence based on risk factors alone, all spine surgery patients should be screened as part of their preoperative workup. Postoperative spine patients that continue to experience musculoskeletal pain should be screened as well. Patients with hypovitaminosis D should be treated according to the Endocrine Society guidelines discussed above, especially since vitamin D treatment is safe and the cost burden low. Furthermore, hypovitaminosis D is not asymptomatic, and symptoms can manifest themselves independent of (or prior to) the musculoskeletal pathological changes associated with conditions like osteomalacia. Published data indicate that hypovitaminosis D could adversely affect bone formation and muscle function in multiple ways. For spinal fusion patients the consequences may include delayed fusion or pseudarthrosis, impaired osseointegration of implanted spinal hardware, prolonged core, and lower limb muscle weakness, and additional stress on implanted hardware and/or adjacent spinal segments. Any of these, as well as hypovitaminosis D-induced neurological changes, may contribute to a spinal fusion patient's persistent postoperative pain; indeed, musculoskeletal pain is a hallmark of hypovitaminosis D. Therefore, it is imperative for spinal fusion patients to maintain sufficient serum 25(OH)D concentrations (i.e., >30 ng/mL). Finally, although hypovitaminosis D is associated with a multitude of adverse health outcomes, vitamin D is not a panacea but rather one critical factor in maintaining musculoskeletal health.
PDF with references is attached at the bottom of this page