Radiograph of patient with distal tibial nonunion with a deformity.


Published 1/1/2008
Annie Hayashi

Patients with nonunions should consult endocrinologists

Study shows 84 percent of patients have metabolic or endocrine abnormalities

Nonunions continue to confound orthopaedic surgeons. Although most fractures respond well to nailing, plating, and other orthopaedic interventions, some defy even the best efforts of surgeons. These problem fractures led Mark R. Brinker, MD, and his colleagues to investigate whether metabolic and endocrine abnormalities were associated with unexplained nonunions.

Dr. Brinker presented the results of his study at the 2007 annual meeting of the Orthopaedic Trauma Association.

Specific nonunion screening criteria
The investigators wanted to determine whether patients who met specific screening criteria had a previously undiagnosed metabolic or endocrine abnormality. The following screening criteria were used:

  • an unexplained nonunion that occurred despite adequate reduction and stabilization without obvious technical error and without any other obvious etiology (26 patients)
  • a history of multiple low-energy fractures with at least one progressing to a nonunion (8 patients)
  • a nonunion of a nondisplaced pubic rami or sacral ala fracture (3 patients)

Patient demographics
Between January 1998 and December 2005, Dr. Brinker saw 683 consecutive patients with nonunions—37 of whom met the screening criteria and were referred to one of two endocrinologists.

The study group included 27 women with an average age of 52 years and 10 men with an average age of 46 years. These patients had undergone an average of 2.4 surgeries.

Most of the nonunions occurred in the femur (16) and tibia (13), but other sites were also involved, including the humerus (4), ankle (4), pubic rami (4), sacral ala (3), radius (1), and ulna (1). Four types of nonunions were identified:

oligotrophic (23), atrophic (12), infected (7), and hypertrophic (4).

Abnormalities were common
Of the 37 patients who met the screening criteria, 84 percent (31 patients) had at least one metabolic or endocrine abnormality. More than two thirds (68 percent) had a vitamin D deficiency; 35 percent had a lack of calcium. Other abnormalities included central hypogonadism, thyroid disorders, and parathyroid hormone disorder.

During the course of the study, the endocrinologist treated the metabolic or endocrine abnormalities while Dr. Brinker provided treatment for the nonunion. Of the 37 patients, 27 had one or more surgeries and 10 were treated nonsurgically.

Vitamin D, calcium resolve nonunion
The positive aspects of referring patients with nonunions to an endocrinologist could be seen in the case study of a 37-year-old patient, who was still experiencing considerable pain 2 years after intramedullary nail fixation of a humeral-shaft fracture. Dr. Brinker removed the nail, trimmed the nonunion site, and performed autogenous posterior iliac crest-bone grafting and plate stabilization with compression applied across the nonunion site.

When, at 6 months postsurgery, radiographs and computer tomography scans showed “persistent nonunion with no cross-sectional area of healing,” the patient was referred to an endocrinologist for evaluation.

The patient was diagnosed with a vitamin D deficiency and prescribed 500 mg of calcium and 800 IU of vitamin D three times per day. Radiographs taken after 5 months of medical treatment showed solid bony union and no need for further surgery. The patient is no longer in pain and is functioning at preinjury levels.

In this study, 30 of 31 patients with newly identified metabolic or endocrine abnormalities attained bony union in an average of 9.6 months after receiving both endocrine and orthopaedic treatment. The patient who did not achieve union, a 20-year-old patient with a subtrochanteric nonunion, vitamin D deficiency, and hyperthyroidism, required a total hip arthroplasty due to inadequate bone stock for revision open-reduction internal fixation.

Eight patients with newly diagnosed metabolic or endocrine abnormalities received endocrine treatment but did not have surgery after the diagnosis. Among these patients, the nonunions resolved in 7.6 months.

The study investigators recommended that patients who have a nonunion that meets their screening criteria be referred for a complete metabolic and endocrine evaluation.

“The study does not prove a causal link between metabolic and endocrine abnormalities and either the development or healing of nonunions,” admitted Dr. Brinker, “but 84 percent of the patients who met our criteria were found to have a metabolic or endocrine abnormality.

“You can bone graft, you can plate them, you can triple plate them. If they don’t have the biologic machinery on a cellular level, they are not going to heal,” he concluded.

Annie Hayashi is the senior science writer for AAOS Now. She can be reached at