When Should You Be Wary Of Hypertrophic Bone Formation?

Author(s): 
By Pamela M. Jensen, DPM

Post-surgical hypertrophic bone formation can be a frustrating problem. It has been identified at fracture, osteotomy and amputation sites. The majority of patients with hypertrophic bone formation are largely asymptomatic and practitioners often identify the condition via radiographs they get for other pathologies. However, those who are symptomatic often have a problematic non-healing wound at the site and can complain of pain, swelling or even decreased range of motion if a joint is involved.
Most of the literature addresses hypertrophic bone formation as a complication associated with acetabular fracture surgery, total hip arthroplasty and below/above knee amputations in children. Yet there is very little literature in the podiatric or orthopedic realm with regard to hypertrophic bone formation in the foot.
Armstrong, et. al., conducted a study of 92 consecutive diabetic patients that confirmed a 45 percent incidence of hypertrophic bone formation two years after patients underwent isolated partial ray amputations. They defined hypertrophic bone formation as bony regrowth of 3 mm or greater, which they noted at the site of a surgical resection or osteotomy of bone.1

What Studies Reveal About The Risk Factors
The etiology of hypertrophic bone formation is largely unknown. However, researchers have determined that surgical or traumatic manipulation of the bone can stimulate factors that may promote overgrowth.2 Known risk factors for hypertrophic bone formation include gender, the location of osteotomy and the type of instrumentation you use. In Armstrong’s study of patients with isolated partial ray amputations, there were some interesting findings in regard to the incidence rates of hypertrophic bone incidence.1
• Fifty-eight percent of male patients had hypertrophic bone.
• When the surgeons performed osteotomies distally to the surgical neck of the metatarsal, 34 percent of the patients had hypertrophic bone.
• When surgeons used manual bone cutting instrumentation, 74.2 percent of the patients experienced hypertrophic bone formation. When they used power instrumentation, 29.5 percent of the patients wound up with hypertrophic bone.1
Upon reviewing the literature, there is no evidence of hypertrophic bone formation in the healing of disarticulation procedures. This phenomenon of bony overgrowth has only been documented in procedures requiring an osteotomy. In addition, osteotomies in the metaphyseal region have a greater incidence of overgrowth.1,2

Looking at it on a microscopic level, you would notice that multi-potential fibroblasts are stimulated by an osteotomy. These fibroblasts produce osteoid, which eventually can result in hypertrophic bone formation. The periosteal layer of hypertrophic bone formation is different from the periosteal layer you would find in normal lamellar bone. Upon maturation, however, hypertrophic bone is histologically identical to normal lamellar bone.3,4 Researchers have also shown that overgrowth occurs from the medullary canal following amputations in young rabbits.5

Review The Diagnostic Indicators For Hypertrophic Bone
You’ve achieved normal amputation stump healing without spur formation when there is cortical bone density across the end of a mature bony stump. On the other hand, hypertrophic bone formation of a stump will show osteopenia and periosteal spurs but no cortical bone density across the medullary canal. Researchers have shown that this growth occurs from the medullary canal.6 The resulting ossification, which is evident on plain film radiographs, occurs approximately one to three months after surgery.4,7,8
When sensate patients have hypertrophic bone following an osteotomy, they will often have symptoms of pain, swelling and erythema. You may also notice a progressive stiffness and decreased range of joint motion during the postoperative period.4 Non-sensate patients will have similar clinical signs (with the exception of pain). Also be aware that these patients are at higher risk from complications, such as plantar ulceration, following a mid-metatarsal amputation. In a study at the University of Texas Health Science Center at San Antonio (UTHSCSA), patients were approximately eight times more likely to reulcerate at the site of ray amputation in the bony overgrowth group.1
In your differential diagnosis, researchers say you should check for post-op infection with osteomyelitis, exuberant periosteal bone formation, heterotopic bone formation and tumor.4 When evaluating non-sensate diabetic patients, you should also include acute Charcot in your differential diagnosis.

At UTHSCSA, we have noted many of the patients who develop hypertrophic bone following a partial foot amputation will also develop a non-healing wound at this site. There is often copious serous drainage from these wounds but cultures and biopsies are negative for soft tissue or bone infection.

Essential Tips On Treatment
We often manage these patients by emphasizing offloading, local care and hyperbaric oxygen but many require revisional amputation. If you suspect hypertrophic bone, you should pursue radiographic evaluation. Findings may include poorly defined radiodense areas without trabecular patterns. These areas of suspect bone enlarge and are continuous with the underlying bone in the form of irregular outgrowths and trabecular architecture. Ossification can occur at some distance from the joint and become attached to the subadjacent bone, forming an exostoses.4
You should reserve treatment for symptomatic cases of pain or recurrent ulceration. Be aware that excising immature bone is associated with a high degree of recurrence in addition to disturbing the periosteum that may control the degree of bone remodeling.1,6 Bone scans are advocated in the literature to determine bone activity. You should not consider surgical intervention until there is substantially decreased uptake.3 When it comes to prophylaxis for heterotropic bone formers, you may include etidronate disodium (Didronel).
You should give etidronate disodium in a dose of 20 mg/kg for one month prior to surgery and three months following the procedure. Researchers have shown that this regimen reduces the formation of hypertrophic bone.6
However, studies have failed to prove the efficacy of etidronate disodium in the treatment of ectopic bone formation secondary to myositis ossificans progressiva.2 A study has revealed that irradiation with 2,000 rads decreases the formation of heterotopic bone if you administer it early in the treatment course.6 Attempts to cap the end of amputations with a variety of metallic, silastic and other synthetic materials have not been consistently successful in eliminating bony overgrowth.6 Many advocate addressing the periosteum when considering any revisional procedure. Some propose using 1 to 2 cm of periosteal stripping while others suggest that you keep the protective envelope intact. This is clearly an area that is worthy of further research.

Final Notes
In conclusion, hypertrophic bone formation can lead to reulceration in diabetic neuropathic patients and can be the cause of complication in elective surgical procedures. Evidence shows that manual instrumentation for osteotomies in metaphyseal bone results in increased trauma to the periosteum and thus increases the risk of over-stimulation of fibroblasts to form hypertrophic bone. You should reserve treatment only for symptomatic cases and hold off on attempting further bone resection until the exostosis is fully matured in order to prevent reoccurrence and further revisional procedures.

Dr. Jensen is a first-year resident at the University of Texas Health Science Center at San Antonio.
Dr. Steinberg (pictured) is an Assistant Professor in the Department of Orthopaedics/Podiatry Service at the University of Texas Health Science Center.

Clarification: The Diabetes Watch column in the April issue was written by Chih Yen, DPM. Dr. Yen is a first-year resident at the University of Texas Health Science Center at San Antonio.




References:

1. Armstrong DG, Hadi S, Nguyen HC, Harkless LB, Factors Associated with Bony Regrowth Following Diabetes-Related Partial Foot Amputation, Journal of Bone and Joint Surgery American, 81(11) 1561-5.
2. Conner JM and Evans DP, Fibrodysplasia ossificans progressiva. Journal of Bone and Joint Surgery 64B: 76-83, 1982.
3. Resnick D, and Niwayama G (eds.) Diagnosis of Bone and Joint Disorders, pp. 2042-2085, 2412-2413, 2997, W. B. Saunders, Philadelphia, 1981.
4. Shollenberger BS, and Mandracchia VJ, Exuberant Bony Proliferation Following Foot Surgery, The Journal of Foot Surgery, Vol. 27, N. 5, pp. 433-439 1988.
5. Hellstadius A, An investigation, by experiments on animals, of the role played by the epiphysial cartilage in longitudinal growth. Acta Chir. Scand. 95:156,1947.
6. Speer DP, The Pathogenesis of Amputation Stump Overgrowth, Clinical Orthopedics and Related Research, No. 159, pp.284-306, September 1981.
7. Turek SL (ed.) Orthopaedics: Principles and their Applications, pp. 744, 1173, J.B. Lippincott, Philadelphia, 1984.
8. Edmonson AS, and Crenshaw AH (ed) Campbell’s Operative Orthopedics, pp. 530, 2372-2375, C.V. Mosby, St. Louis.

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