Radiographic time to union of distal radius fractures slightly longer with bisphosphonate use

Issue: May 2010

Patients receiving bisphosphonates at the time of surgery healed, on average, 6 days later than those not receiving bisphosphonates.

Bisphosphonate use and surgical treatment were associated with a slightly longer time to radiographic union in patients with distal radius fractures, according to data presented at the 2010 Annual Meeting of the American Academy of Orthopaedic Surgeons in New Orleans.

“Effects on fracture healing of these medications are poorly understood,” said Tamara Rozental, MD, of the Beth Israel Deaconess Medical Center in Boston. “Some studies have shown that early callus formation is not affected at all, some have shown there is delayed remodeling, and others have actually shown enhanced fracture healing, so the data is very heterogenous.”

Comparative study

Tamara D. Rozental, MD
Tamara Rozental

Because of these inconsistent findings, Rozental and her colleagues conducted a study comparing radiographic healing among 43 patients who were receiving bisphosphonate therapy at the time of treatment for distal radius fractures and 153 fracture patients who were not receiving bisphosphonates at the time of treatment. The researchers excluded patients younger than 50 years and those with multitrauma or polytrauma fractures. Demographic data were similar between the two groups, except for sex: The group of patients receiving bisphosphonates included predominantly women with only one man in the group.

The researchers defined radiographic union as “bridging of callus across fracture lines in at least two cortices,” and determined the time to union based on the date of the closed or open treatment and the date of the first radiograph that met union criteria.

Most patients (86%) were receiving alendronate [Fosamax, Merck] with 14% receiving risendronate [Actonel, Sanofi Aventis], Rozental said. All patients started bisphosphonate therapy at least 1 month before fracture. Average treatment duration was 25 months; 33 patients were receiving bisphosphonates for longer than 1 year.

No correlation

All patients achieved union, although one patient in the bisphosphonate group had a delayed radiographic union, which Rozental said was clinically healed before the radiographs showed a bridging callus. Time to union was 58 days in the bisphosphonate group, and 55 days excluding the patient with the delayed union. In the control group, time to union was 49 days, yielding a 6-day difference (P=.02).

“However, the small differences in healing times — less than 1 week — are not considered clinically relevant,” Rozental told Orthopedics Today. In some cases, patients can be clinically healed before radiographic criteria are met and animal studies have shown that bisphosphonates can inhibit callous remodeling without affecting its mechanical integrity. For these reasons, radiographic healing may lag between clinical healing in these patients.

Linear regression analysis revealed that bisphosphonate use (P = .02) and surgical treatment (P = .03) were both associated with longer times to union, but age, sex, fracture severity and comorbidities were not. Bisphosphonate use was also associated with longer time to healing after the researchers separately controlled for age (P = .02), sex (P < .05), fracture complexity (P= .02) and comorbidities (P = .03), and after they controlled for age, sex and treatment type (P = .004). After the researchers controlled for bisphosphonate use, they found that operative fracture fixation was associated with longer healing time (P = .02). They did not find any correlation between duration of bisphosphonate use and time to healing or between osteoporosis status and time to healing.

“Although further studies are needed to better define the effects of bisphosphonate therapy on fracture healing, our results suggest that bisphosphonate therapy can be continued after distal radius fractures without deleterious effects,” Rozental said. — by Tina DiMarcantonio

References:

Rozental TD, Vazquez MA, Chacko A, et al. Comparison of radiographic fracture healing in the distal radius for patients on and off bisphosphonate therapy. J Hand Surg. 2009;34A:595-602.

Rozental TD, Vazquez MA, Chacko A, et al. Radiographic fracture healing in the distal radius for patients on and off bisphosphonate therapy. Paper 079. Presented at the 2010 Annual Meeting of the American Academy of Orthopaedic Surgeons. March 9-13, 2010. New Orleans.

Tamara D. Rozental, MD, can be reached at the Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Stoneman 10, Boston, MA 02215; 617-667-3940; e-mail: trozenta@bidmc.harvard.edu.

The early 1960s saw numerous basic research articles regarding diphosphonates (now called bisphosphonates), especially EHDP[Didronel]. Many effects were noted regarding inhibitory activity of calcium phosphate precipitation, one being preventing calcification of osteoid. This lead to Didronel’s use to prevent heterotopic ossification (HO) at a dosage of 20 mg/kg in the ‘70s and early ‘80s. What seems to be neglected, however, is that EHDP also inhibited normal mineralization of bone. Furthermore at this dosage, dog femurs began to fracture at 9 months.

It was also noted at a lower dosage, 10 mg/kg, the drug “poisoned “ osteoclasts. It did not destroy them but slowed their metabolism. If the drug was stopped, the osteoclasts returned to their normal function. Consequently this drug was also briefly used to treat osteoporosis. “Drug holidays” were also recommended to allow the bone and osteoclasts to return to some physiologic normalcy.

Many clinicians were not cognizant of the basic research, proper dosage or duration of treatment due to the duality of mechanisms of the drug. A 1985 article published in the Journal of Bone and Joint Surgery, for example, stated the drug was not effective in preventing HO after total hip arthroplasty. Unfortunately the authors used 10mg/kg which would not be expected to prevent HO formation.

The risk-reward ratio strongly favors the continued use of bisphosphonates in the treatment of osteoporosis. However, the drug is not benign. It is most likely responsible for spontaneous subtrochanteric fractures and possibly decreased fracture healing. The orthopedist must be vigilant and seek guidelines for its continued use.

– Douglas Garland, MD
Orthopedics Today Editorial Board member

Reference:

Thomas BJ, Mankin HJ. Results of the administration of diphosphonate for the prevention of heterotopic ossification after total hip arthroplasty. J Bone Joint Surg (Am). 1985. 67:400-403.