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Factors Associated with Bone Regrowth Following Diabetes-Related Partial Amputation of the Foot*

D. G. ARMSTRONG, D.P.M., S. HADI, D.P.M., H. C. NGUYEN, D.P.M. and L. B. HARKLESS, D.P.M., SAN ANTONIO, TEXAS

Investigation performed at the Department of Orthopaedics, University of Texas Health Science Center at San Antonio, San Antonio

	Abstract

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Background: The formation of hypertrophic bone after partial resection of metatarsal bone has the potential to cause abnormal foci of high pressure in people who have diabetes mellitus; this may increase the risk of reulceration and reamputation. However, we are not aware of previous studies evaluating the risk factors for this entity. Methods: The records of ninety-two adults (mean age, 54 ± 10.1 years; range, thirty to seventy-four years) with diabetes who had had an isolated partial amputation of a ray were abstracted. Repeat radiographs were made for all of these subjects at a mean of 22 ± 6.1 months (range, thirteen to thirty-five months) after the initial procedure. The formation of hypertrophic bone was defined as more than three millimeters of regrowth. Results: A total of forty-one (45 percent) of the subjects had formation of hypertrophic bone at the time of radiographic analysis after isolated partial amputation of a ray. On multivariate analysis, the factors that were significantly associated with this regrowth of bone were male gender (88 percent [thirty-six] of the forty-one patients who had bone regrowth were male compared with 51 percent [twenty-six] of the fifty-one patients who did not have bone regrowth; p < 0.01, odds ratio = 5.7, 95 percent confidence interval = 1.8 to 18.9), the use of manual bone-cutting instruments (used in 56 percent [twenty-three] of the forty-one patients who had bone regrowth compared with 16 percent [eight] of the fifty-one who did not; p < 0.01, odds ratio = 4.7, 95 percent confidence interval = 1.6 to 13.8), and a resection made distal to the surgical neck of the metatarsal (used in 34 percent [fourteen] of the forty-one patients who had bone regrowth compared with 12 percent [six] of the fifty-one who did not; p < 0.03, odds ratio = 4.5, 95 percent confidence interval = 1.2 to 16.9). The patients who had regrowth of bone were approximately eight times more likely to have reulceration at the site of the amputation than were those who did not have regrowth (24 percent [ten] of the patients with regrowth had reulceration compared with 4 percent [two] of the patients without regrowth; p < 0.01, chi square = 8.4, odds ratio = 7.9, 95 percent confidence interval = 1.6 to 38.5). Conclusions: Overgrowth of the bone of a transected metatarsal predisposes patients to ulceration. Male gender, the use of manual bone-cutting instruments, and metaphyseal amputation may be associated with long-term regrowth of bone following isolated partial amputation of a ray. The use of power instruments during these procedures may lead to a lower prevalence of this reaction, thereby potentially reducing the risk of ulceration, infection, and reamputation.

	Introduction

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Complications of the foot in patients with diabetes are the most common underlying cause of nontraumatic amputation of a lower extremity^5,27. Individuals with diabetes have a fifteen to forty-six-fold greater risk of amputation than do those without diabetes^4,27, and ulceration of the foot is the most consistent predisposing finding for the loss of a limb in the diabetic population. Therefore, the treatment and prevention of ulcers are the focus of amputation-prevention programs^7,24,29. Neuropathic ulcers usually develop in areas on the sole of the foot that have been exposed to moderate-to-high pressures during normal walking^10,15. Subjects with neuropathy but without a portal for the entry of bacteria rarely have infections. Furthermore, in the absence of critical ischemia, patients who do not have an ulcer rarely need an amputation²⁴.

Similarly, once a patient has had an amputation at the level of the foot, he or she is as much as thirty-six times more likely to have an ulcer on that foot than is an individual who did not have an amputation²⁴. It has been well documented that patients with diabetes have contractures of the digits and subsequently have elevated peak plantar pressures secondary to these contractures and retrograde plantigrade buckling of the metatarsals following isolated partial resection of the ray or the digit^22,31. We previously reported that a group of twenty-seven patients with diabetes who had had partial amputation of the foot had peak pressures in the forefoot that were nearly 30 percent higher than those of an age and gender-matched control group of 150 patients with diabetes⁹. We observed that many of these patients had radiographically evident formation of hypertrophic bone that had resulted in prominent exostoses or an abnormal metatarsal length pattern that may have caused or accentuated a focus of high pressure. Certainly, the ability to identify clinical or technical factors associated with overgrowth of bone at sites of partial amputation of a foot could assist the clinician in mitigating the severity of this complication. The literature contains a number of case reports, small case series, and discussions associated with the regrowth of bone following a proximal-level (transtibial or transfemoral) amputation of a lower extremity^{1,2,14,16,21,28,30,37}. However, these studies specifically addressed procedures performed on patients who were less than eighteen years of age. We are not aware of any report in the medical literature evaluating factors associated with this complication in adults with diabetes who had been managed with an amputation at the level of the foot. Therefore, the purpose of the present study was to assess the factors associated with overgrowth of bone following isolated partial amputation of a ray in adults with diabetes.

	Materials and Methods

Top Abstract Introduction Materials and Methods Results Discussion References

 
We abstracted the records of ninety-two consecutive adults (mean age, 54 ± 10.1 years; range, thirty to seventy-four years) with diabetes who had had an isolated partial amputation of a ray. All of the amputations were performed to eradicate infection. As part of the protocol, patients who are managed in high-risk diabetic foot clinics for complications of the foot have a standardized evaluation to assess the wounds and their severity¹¹, sensory neuropathy⁸, vascular insufficiency³⁸, and infection.

The diagnosis of diabetes mellitus was verified for all of the patients with use of the criteria set forth by the World Health Organization⁴¹, which include treatment with insulin or oral administration of a hypoglycemic agent, two random blood-glucose measurements of more than 200 milligrams per deciliter (11.1 millimoles per liter), or a level of fasting blood glucose of more than 140 milligrams per deciliter (7.8 millimoles per liter). According to these criteria, the subjects had had diabetes for a mean duration of 11.5 ± 5.1 years (range, one to twenty-four years). Sensory neuropathy was evaluated with a ten-gram Semmes-Weinstein monofilament wire and a Bio-Thesiometer (Bio-Medical Instrument, Newbury, Ohio) according to previously described criteria^8,12. All of the subjects had an absent protective threshold according to these criteria.

Repeat radiographs were made for all of the subjects at a mean of 22 ± 6.1 months (range, thirteen to thirty-five months) after the initial procedure. The formation of hypertrophic bone was defined as more than three millimeters of regrowth apparent on any two radiographic projections (standard dorsoplantar, medial oblique, or lateral).

For the purposes of analysis, we dichotomized several variables. The level of the amputation of the ray was defined as metaphyseal (distal to the surgical neck of the metatarsal) or diaphyseal. Renal function was stratified as no albuminuria (less than twenty micrograms of albumin per minute) or microalbuminuria (twenty to 200 micrograms of albumin per minute) as opposed to macroalbuminuria (more than 200 micrograms of albumin per minute) or chronic renal insufficiency (more than 4.0 milligrams of creatinine per deciliter [354 micromoles per liter], current dialysis, or a history of renal transplantation), with this last stage considered advanced nephropathy^20,35. Peripheral vascular disease of the lower extremity was evaluated with use of several dichotomous variables. The criteria for such a diagnosis included the absence of palpable dorsalis pedis and posterior tibial arteries in the foot, transcutaneous oxygen tension on the dorsal aspect of the first intermetatarsal space of less than thirty millimeters of mercury (4.00 kilopascals)²⁶, and an ankle-brachial systolic blood-pressure index of less than 0.80¹³. Tobacco use was defined as any past or present use. The degree of control of the glucose level was analyzed both continuously and dichotomously. We defined poor control as a level of glycosylated hemoglobin of more than 9 percent at the time of admission to the hospital. Lastly, we defined obesity as a body-mass index of more than thirty kilograms per square meter (Table I).

	Results

Top Abstract Introduction Materials and Methods Results Discussion References

 
Forty-one (45 percent) of the ninety-two subjects had hypertrophic bone formation at the time of radiographic analysis after the isolated partial amputation of the ray. On univariate analysis, the factors that were significantly associated with this regrowth included male gender (88 percent [thirty-six] of the forty-one patients who had bone regrowth were male compared with 51 percent [twenty-six] of the fifty-one patients who did not have bone regrowth; p < 0.01, chi square = 14.0, odds ratio = 6.9, 95 percent confidence interval = 2.3 to 20.4), the use of manual bone-cutting instruments (used in 56 percent [twenty-three] of the forty-one patients who had bone regrowth compared with 16 percent [eight] of the fifty-one who did not; p < 0.01, chi square = 16.6, odds ratio = 6.8, 95 percent confidence interval = 2.6 to 18.1), and a resection made distal to the surgical neck of the metatarsal (used in 34 percent [fourteen] of the forty-one patients who had bone regrowth compared with 12 percent [six] of the fifty-one who did not; p < 0.02, chi square = 6.7, odds ratio = 3.9, 95 percent confidence interval = 1.3 to 11.3). With the numbers available for study, we could not detect a significant association between regrowth and age, the degree of control of the glucose level, renal disease, body-mass index, nutritional status, peripheral vascular disease, or previous amputation. On multivariate analysis, male gender (p < 0.01, odds ratio = 5.7, 95 percent confidence interval = 1.8 to 18.9), the use of manual bone-cutting equipment (p < 0.01, odds ratio = 4.7, 95 percent confidence interval = 1.6 to 13.8), and the level of metaphyseal amputation (p < 0.03, odds ratio = 4.5, 95 percent confidence interval = 1.2 to 16.9) continued to be strongly associated with regrowth of bone (Spearman's correlation coefficient = 0.4) (Table II).

	Discussion

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The results of the present study suggest that osseous overgrowth of a metatarsal after partial transection predisposes a patient to ulceration. Furthermore, male gender, the use of manual bone-cutting instruments, and metaphyseal amputation may be associated with regrowth of bone following isolated partial amputation of a ray. We were surprised to find that the patients in whom the resection had been performed with manual equipment had a significantly higher prevalence of regrowth of bone than did those in whom the procedure had been performed with power equipment (p < 0.05). Although we are not aware of other studies in the literature in which the use of manual equipment was compared with the use of power equipment for amputations at the level of the foot, we hypothesized that the use of manual bone-cutting instruments crushes or strips the periosteum to a greater extent than does the appropriate use of power equipment. In a study of 144 rats, Hernández et al.¹⁹ found a significant difference in longitudinal bone growth and metaphyseal modeling in femora subjected to mid-diaphyseal periosteal stripping compared with nonstripped femora (p < 0.05). This finding was associated with a lower osteoclastic index in the external metaphyseal surface and a lower rate of bone formation in the internal surface of the metaphyseal cortex when the periosteum was left intact. Those authors concluded that intact periosteum may play a role in controlling metaphyseal remodeling. Although the data in the present study do not support these conclusions directly, we believe that the findings in our study deserve further investigation.

The level of the resection of the ray also appeared to play an important role in the regrowth of bone. We found that patients were nearly four times more likely to have regrowth of bone if the resection had been made distal to the surgical neck of the metatarsal (p < 0.03). This association supports the findings of O'Neal et al.²⁸, who reported, in a retrospective study of proximal-level amputations in children, that metaphyseal amputations were associated with a slightly higher prevalence of regrowth compared with diaphyseal amputations.

The apparent association of male gender with the formation of hypertrophic bone was not surprising, as men appear to be invariably linked to a host of other factors that place them at higher risk for ulceration and amputation. Other investigators detailing the sequelae of diabetic neuropathy of the lower extremity, such as ulceration, Charcot fracture, puncture wounds, and mortality after amputation, have compared responses by gender. In general, women seem to have fewer complications and a better prognosis than men do. In a longitudinal study, we revealed that the time to reach quiescence after treatment for acute Charcot arthropathy was nearly 30 percent shorter for women than for men (p < 0.008)⁶. Similarly, in another study, superficial neuropathic ulcers of the plantar aspect of the foot took significantly less time to heal in women (p < 0.05)³⁹. In a retrospective study of infected puncture wounds, more than twice as many diabetic men and nearly four times as many nondiabetic men needed emergent incision and drainage of infected puncture wounds than did their female counterparts⁴. Lavery et al.²³ reported that the age-adjusted mortality rate after amputation of a toe or foot was higher for diabetic male patients than for diabetic female patients. There are numerous factors that may play a role in the impact of gender on morbidity of the lower extremities. These factors may include level of activity, degree of compliance, level of denial, strength of social support mechanisms, and quality of education as well as frequency and severity of arterial occlusive disease, neuropathy, and diabetes control. None of these factors, however, can be directly linked to the regrowth of bone after an amputation. Thus, again, further investigation is needed.

In conclusion, the life spans of people in both industrialized and nonindustrialized nations are increasing and, as a consequence, the prevalence of diseases such as diabetes is increasing as well^{3,17,18,25,32,33}. It may, then, be postulated that individuals will be living longer with many end-stage complications of diabetes, including partial amputation of a foot³⁴. The results of the present study suggest that there may be factors associated with the potential for recurrence of pathological lesions following an amputation at the level of the foot. If this is the case, it may be possible to intervene initially or prophylactically to prevent the progression of sequelae that are profoundly limb-threatening.

	Footnotes

 
*No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. No funds were received in support of this study.

Department of Orthopaedics, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78284-7776. E-mail address: armstrong@usa.net (Dr. Armstrong).

	References

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This Article Abstract Full Text (PDF) Free Letters to the Editor: Submit a response Alert me when this article is cited Alert me when Letters to the Editor are posted Alert me if a correction is posted Services E-mail this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My File Cabinet Download to citation manager Rights and Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by ARMSTRONG, D. G. Articles by HARKLESS, L. B. Search for Related Content PubMed PubMed Citation Articles by ARMSTRONG, D. G. Articles by HARKLESS, L. B. Social Bookmarking                   What's this?

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