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Home , Bone health, Nonunion

CHAPTER 4 5 RISK FACTORS

Stephan J. LaPointe, DPM, PhD Dan Perez, DPM Stephanie Bullock, MA

Nonunions secondary to fractures and failed arthrodesis middle, and late (12, 13) phases of healing. One will be discussed. Co-morbidities, medications, and retrospective study showed increased time to healing of iatrogenic, patient induced factors leading to femur fractures in a group of patients over 65 with will be reviewed. at a mean of 19.4 weeks versus sub 40-year-old patients with normal bone mineral density at 16.2 weeks CO-MORBIDITIES (14). Another prospective randomized trial involving 113 patients showed increased rate of nonunion and Due to the nature of the podiatric profession and prevalence complications with 76% of the 33 failures occurring in of the disease, is likely to be the most common patients with osteoporosis (15). co-morbidity that will be involved in the patient that devel- As podiatrists, we should also be alerted to the ops a nonunion in our practices. The American Diabetes possibility of insufficiency fractures of the calcaneus in the Association’s 2007 National Diabetes Fact Sheet states the absence of trauma (16) in patients with osteoporosis. These disease affects 7.8% or 23.6 million Americans. Diabetes patients will typically present with “ankle” pain with retards . It has been shown that the glycation tenderness noted along the superior-lateral aspect of the end products found in diabetes can retard bone healing calcaneus with positive bone scan and magnetic resonance between 40 to 60% (1). In the experimental animal model imaging and negative radiology findings for up to 2 months. peri-implant bone was shown to be significantly decreased in Rheumatoid arthritis has increased risk for osteoporosis two studies (2, 3) and another showed significantly secondary to both the disease process and its treatment in decreased healing of tendon to bone in the rotator cuff. The the form of prednisone and methrotrexate. There is a strength of bone in fracture healing in the experimental rat correlation between bony erosions and decreased bone model has been shown to be reduced in two studies (4, 5). mineral density leading to higher risk for fracture (17). A In the diabetic patient population both tibial pilon fractures recent study has also implicated glycation end products and ankle fractures have shown increased complication rates similar to those seen in the diabetic patient for the that included nonunion and delayed union (6, 7). Studies osteoporosis seen in the rheumatoid population (18). are currently underway to evaluate the efficacy of fibroblast Several retrospective studies have looked at fusion rates growth factors in increasing bone growth in diabetes and in the rearfoot. Relative to the ankle fusions one author osteoporosis and early results are promising (8, 9). This line published two separate papers. In one, a series of 25 tibio- of research may eventually lead to the discovery of other calcaneal fusions with a retrograde intramedullary nail treatment options for this subset of patients and ultimately resulted in one nonunion and three deep (19). all patients at risk for non-union (8). The second study reviewed 35 ankle fusions 13 performed As baby boomers age, the increase in the elderly percutaneously and 22 open fixated with compression population will lead to an increase of osteoporosis in the screws. Nine went on to nonunions with no difference podiatric practice. Osteoporosis strikes many subsets of between the open versus percutaneous groups. Citing the the world population, including women, the elderly, and nonunion rates and decreased patient satisfaction the authors those with arthritis, autoimmune diseases, HIV, and the did not recommend compression screw fixation for ankle immuno-compromised. This disease predisposes people to fusion in the rheumatoid population. Another retrospective an increased risk of low trauma and fragility fractures and study of 32 ankle fusions compared the rate of fusion with increases the likelihood for nonunions. Approximately 40% (19) versus via 6.5 of white women and 13% of white men ages 50 years will millimeter cancellous compression screws (13). They had have a fragility or insufficiency fracture secondary to four failures all secondary to in the external osteoporosis in the US. Studies using the rat model have fixation group. Three failed to fuse with one secondary to shown decreased healing potential in the early (10, 11), infection in the internal fixation group. They found no 240 CHAPTER 2 differences in fusion rates or complications comparing the hypocalcemia can be addressed and in most cases will reverse two groups (20). The tibio calcaneal nail was modified with the . Conversely, parathyroidectomy four fins in the calcaneus and inserted in 15 ankles without and hypoparathyroidism and pseudohypoparathyroidism a nonunion and two wound complications (21). result in hypocalcemia and negative changes in bone. Another study using a Kuntscher tibio-calcaneal nail and Vitamin D plays an important role in . early mobilization had an 80% fusion rate with two Rickets, a childhood disease, and the adult form, nonunions in eleven. Triple arthrodesis with staple fixation , are secondary to malnutrition with decreased and autologous had a 100% successful fusion and Vitamin D are more often seen in developing in 32 feet with all patients relating they would have the countries. However, we are now seeing more cases of procedure again (22). Arthrodesis rates although generally rickets in the US and Europe. There is also a rise in acceptable in the rheumatoid patient do present with subclinical Vitamin D deficiency especially in the colder increased complications and as expected somewhat higher climates and during the winter months. There is increased failure rates. attention being given to the role that subclinical Vitamin D Primary hyperparathyroidism, although rare at deficiency is playing in bone health, increased fracture risks 100,000 cases or 1 in 2,719 Americans, can lead to in both the clinical and laboratory setting. Within the last significant bone loss and hypercalcemia. As the name few years three major laboratories have seen significant implies this disease is of the hyperparathyroid gland due increases in testing with increases of 74% (Mayo Clinic), 80% to adenoma, hyperplasia, or less likely carcinoma of the (Quest) and 90% (LabCorp). One prospective study parathyroid gland. This population will have elevated compared Vitamin D levels in controls of age-matched 41 and calcium levels secondary to inpatient and 41 outpatient males and 41 increased . patients. Subclinical Vitamin D (defined as <50 nmol/L Secondary hyperparathyroidism occurs when the serum 25-hydroxyvitamin D) was 63% in the fracture group, parathyroid is responding to decreased calcium or increased compared with 25% in the control groups. The investigators phosphate levels. The most common cause for this is chronic concluded that subclinical Vitamin D deficiency and renal failure. Failing kidneys do not convert enough resulting secondary hyperparathyroidism was the leading risk Vitamin D to its active form and do not adequately excrete factor for hip fractures compared to age, body weight, phosphorus both leading to hypocalcemia. This in turn tobacco, comorbidity, corticosteroids, and alcohol (24). stimulates the parathyroid glands leading to increased bone Osteogenesis imperfecta, a genetic disorder resorption. Other causes for secondary hyperparathyroidism compromising the connective tissue structure secondary to include malabsorption of calcium found in chronic malformed Type I , results in a very high nonunion pancreatitis, small bowel disease, and more often now with rate (25-28). Paget’s disease or what is now called bariatric surgery specifically gastric bypass. Long term osteodystrophia deformans is an inflammatory reaction lithium use will also cause decreased calcium levels and the possibly secondary to a virus results in a three phase reaction secondary form. in bone. Increased osteoclastic activity is followed by a mixed Finally tertiary hyperparathyroidism occurs when the clastic and blastic cycle and ultimately a burned out phase parathyroid has been up-regulated for a long time even if the where there is hyperdense bone. Many patients may be original insult is corrected as is sometimes seen following subacute and not symptomatic. They will have elevated transplant. In these cases the parathyroid hypertrophy alkaline phosphatase levels with normal calcium and is irreversible. Regardless of the cause of the overactive phosphate levels. By itself this is not a direct contraindication parathyroid the hormone secreted leads to decreased bone to surgery, but the surgeon must bear in mind that the density. One study addressed the incidence of secondary disease process does alter bone remodeling and results in a hyperparathyroidism in postmenopausal females about to higher complication rate. undergo total knee replacement. They evaluated renal As podiatrists we are acutely aware of the role the function, intact parathyroid hormone, calcium and vascular system plays in lower extremity healing and phosphorous levels and found 35% of these patients to have pathology. We screen all our patients for peripheral secondary hyperparathyroidism. They recommended pre- vascular disease; however, we must also consider the role operative screening for elevated intact parathyroid hormone of anemia and any myelodysplasias (29-32), which can before total knee replacement (23). Certainly, many of our either slow or prevent bone healing. Although clinical data patients will tell you that they have compromised kidney was lacking, one prospective randomized experimental study function and should have this evaluated for secondary induced anemia in the rat model and demonstrated hyperparathyroidism before proceeding. The underlying significantly reduced osteogenesis in the anemia model (29). CHAPTER 2 241

PATIENT DERIVED RISK FACTORS formation at periosteal and cancellous sites (42). One retrospective study showed increase healing time in As of 2005, the US Department of Human Services tranvserve tibial fractures in alcohol abusers (43). A reported that just over 20% of Americans or 45 million meta-analysis performed in 2007 showed that consuming Americans smoked tobacco. Tobacco use is the single most 0.5 to 1.0 servings of alcohol per day had a lower hip devastating user-controlled health risk. One study showed fracture rate then abstainers but 2.0 servings per day an increase in nonunion rate for hindfoot fusions at 2.7 increased hip fracture rates. Interestingly, there was times the rate than in non smokers. The same study found a increased bone mineral density with alcohol use but residual increase in those who quit smoking, albeit decreased because the reviewed articles failed to stratify the amount when compared to those who continued to smoke, in of alcohol it could not determine if higher consumption nonunion rates (33). Using the Austin bunionectomy as an resulted in decreased density (44). elective surgical model and radiographic bone healing as the A form of iatrogenic osteoporosis we also need to criteria, Krannitz et al found that in the smoking population consider is disuse whenever we require time to bone healing was 1.7 times longer (34). There is no immobilization and/or nonweight bearing. Aggressive paucity of data on the negative effects of tobacco on bone return to activity may result in fractures. There have been healing, fractures and arthrodesis in both the animal model cases of calcaneal and tibial stress fractures reported in the and patient population. It behooves the podiatric surgeon literature following treatment for acute leg fractures. to seriously consider the possible sequela of nonunion in the Certainly other causes of disuse osteopenia must also be smoking population. In the author’s practice all fusion considered such as hemiplegia following stroke, spinal cord procedures involving the midfoot and proximal require that injuries or any condition that may immobilize the patients. the patient quit smoking prior to surgical intervention. All This can also increase risk of nonunion secondary to patients undergoing surgery are advised of the increased risk the osteoporosis. of tobacco use on bone and wound healing. The correlation between obesity and bone quality or REFERENCES osteoporosis is currently under investigation with data showing equivocal results. One recent animal model found 1. Santana RB, Xu L, Chase HB, Amar S, Graves DT, Trackman PC. 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