Published 6/1/2013
Maureen Leahy

Metabolic Workup Can Be Key to Healing Certain Nonunions

Correcting metabolic or endocrine abnormalities can lead to solid bony union

Certain fracture nonunions can heal without surgical intervention, if the underlying metabolic or endocrine abnormalities are corrected, according to Mark R. Brinker, MD, of Fondren Orthopedic Group and Texas Orthopedic Hospital, Houston.

During his presentation on “The Missing Info…How to Do the Metabolic Workup,” Dr. Brinker pointed out that metabolic and endocrine abnormalities—including vitamin D deficiency/insufficiency, calcium imbalance, thyroid problems, hypogonadism, and hyperparathyroidism—have been implicated with nonunion and fracture risk.

“Some fractures fail to unite despite excellent fixation in a seemingly healthy host with good local biology. It’s important to determine what’s inhibiting bone healing in these patients,” he told attendees of the Orthopaedic Trauma Association’s Specialty Day.

Metabolic-endocrine workup, treatment
Dr. Brinker recommended an extensive metabolic-endocrine workup (
Table 1) for patients who have the following:

  • A persistent nonunion despite adequate treatment without obvious technical error
  • A history of multiple low-energy fractures with at least one progressing to a nonunion
  • Nonunion of a nondisplaced pubic rami or sacral ala fracture

Once an abnormality is identified, treatment should be appropriate to the diagnosis, he noted. For example, patients with insufficient or deficient levels of vitamin D should be treated with supplemental vitamin D and calcium. Vitamin D insufficiency is commonly defined as a 25-hydroxyvitamin D [25(OH)D] level of less than 30 ng/mL; deficiency is defined as a 25(OH)D level of less than 20 ng/mL.

“Vitamin D deficiency/insufficiency is a big problem, affecting 40 percent to 50 percent of the U.S. population,” Dr. Brinker said. In a study he published in 2007, 31 of 37 (84 percent) of patients with nonunions had undiagnosed metabolic or endocrine abnormalities, and nearly 70 percent of those patients were vitamin D deficient or insufficient.

In some patients, hormone replacement therapy or bisphosphonates may also be indicated, according to Dr. Brinker. Although no proven relationship exists between fracture healing and androgen deficiency, he said he frequently sees evidence that supports an association between the two.

“I work closely with an endocrinologist and we treat low levels of androgen by titrating the testosterone dose to a normal value based on the patient’s age,” he said. He cautioned, however, that prolonged bisphosphonate use in women can lead to stress fractures.

Surgery not always necessary
According to Dr. Brinker, in certain nonunions, medical treatment alone can result in progression to solid bony union, with mechanical stability generally an important prerequisite.

“In our study, 8 patients with well-established nonunions who had newly diagnosed metabolic or endocrine abnormalities healed following medical treatment alone, without surgical intervention,” he said.

In one case, a 57-year-old woman, who was still experiencing considerable pain 6 months after receiving surgical treatment outside the United States for a greater tuberosity fracture of the proximal humerus, was referred for an endocrinology evaluation. The patient had a borderline low level of vitamin D and was prescribed 3,000 IU of vitamin D and 1,500 mg of calcium per day. After 3.5 months of treatment and no surgery, the patient was pain free and radiographs showed solid bony union.

Dr. Brinker noted that metabolic bone diseases or disorders do not necessarily cause nonunion, but that treating such disorders may aid in bone healing. He advocates evaluating certain patients with nonunions for endocrine or metabolic abnormalities as a standard of care and believes that screening all patients with nonunions—and perhaps some patients with fractures—may be warranted in the future.

“As orthopaedic surgeons, we need to become skilled at knowing which patients to refer for in-depth endocrinology evaluation and treatment,” he said. “But the most important take-home message is this: Certain nonunions can be healed by correcting metabolic and endocrine abnormalities, without surgical intervention.”

Disclosures: Dr. Brinker—Journal of Orthopaedic Trauma section editor.

Maureen Leahy is assistant managing editor of AAOS Now. She can be reached at leahy@aaos.org


  1. Metabolic and Endocrine Abnormalities in Patients with Nonunions (J Orthop Trauma 2007; 21:557-570)

Bottom Line

  • Despite excellent fixation in seemingly healthy patients with good local biology, some fractures fail to unite.
  • Metabolic and endocrine abnormalities have been implicated with nonunion and fracture risk.
  • Patients with nonunion who meet specific criteria should be evaluated for endocrine or metabolic abnormalities.
  • Certain nonunions can be healed by correcting metabolic and endocrine abnormalities, without surgical intervention.