Tag Archive | bisphosphonates

JBJS Editor’s Choice: Improving Function After Fragility Fractures

hip_fracture_drugs_11_16_16In the past several years, the orthopaedic community has become highly engaged in improving the follow-up management of patients presenting with fragility fractures. We have realized that orthopaedic surgeons are central to the ongoing health and welfare of these patients and that the episode of care surrounding a fragility fracture represents a unique opportunity to get patients’ attention. Using programs such as the AOA’s “Own the Bone” registry, increasing numbers of orthopaedic practices and care centers are leading efforts to deliver evidenced-based care to fragility-fracture patients.

In the November 16, 2016 edition of The Journal, Aspenberg et al. carefully examine the impact of the anabolic agent teriparatide versus the bisphosphonate risedronate on the 26-week outcomes of more than 170 randomized patients (mean age 77 ±8 years) who were treated surgically for a low-trauma hip fracture. This investigation is timely and appropriate because our systems of care are evolving so that increasing numbers of patients are receiving pharmacologic intervention for low bone density both before and after a fragility fracture.

The secondary outcomes of the timed up and go (TUG) test and post-TUG test pain were better in the teriparatide group, but there were no differences in radiographic fracture healing or patient-reported health status.

Although this study was designed primarily to measure the effects of the two drugs on spinal bone mineral density at 78 weeks, these secondary-outcome findings confirm the value of initiating pharmacologic intervention early on after a fragility fracture, whether it’s a bisphosphonate or anabolic agent. The orthopaedic community needs to continue leading multipronged efforts to deal with the public health issues of osteoporosis and fragility fractures.

Click here for additional OrthoBuzz posts related to osteoporosis and fragility fractures.

Marc Swiontkowski, MD
JBJS Editor-in-Chief

Atypical Femoral Fractures: An Update

F2.mediumWe posted our first “Case Connections” article about  bisphosphonate-related atypical femoral fractures (AFFs) one year ago. Since then, JBJS Case Connector has published three additional case reports on the same topic, suggesting that it’s time for a revisit. These three recent cases demonstrate that AFFs can occur despite prophylactic intramedullary (IM) nailing of an at-risk femur, that AFFs can present as periprosthetic fractures, and that men taking bisphosphonates—not just women—can experience AFFs.

What’s New in Limb Lengthening/Deformity Correction: Level I and II Studies

Every month, JBJS publishes a Specialty Update—a review of the most pertinent and impactful studies published in the orthopaedic literature during the previous year in 13 subspecialties. Here is a summary of selected findings from Level I and II studies cited in the August 19, 2015 Specialty Update on limb lengthening and deformity correction:

Pediatric Disorders and Trauma

–A modified guided-growth technique for insertion of tension-band plates decreased operative time, radiation exposure, and incision size.1

–Two meta-analyses concluded that, although oral or intravenous bisphosphonates in children with osteogenesis imperfecta increased bone mineral density, evidence of reduction in fracture rates was inconclusive.2, 3

–A systematic review of 40 studies on surgical management of posttraumatic cubitus varus in children noted an overall complication rate of 14.5%, with no single technique being substantially safer or more effective.4

 Lower-Limb Trauma/Reconstruction in Adults

–A prospective randomized study on the surgical treatment of complex knee dislocations with ligament reconstruction found a significantly lower risk of delayed ligament failure with adjunctive hinged external fixation compared with a hinged knee brace.

–A prospective randomized study comparing biplanar external fixation with reamed interlocking intramedullary nailing for treating open tibial shaft fractures found similar healing rates and functional outcomes one year postoperatively.5

–Patients with extra-articular distal tibial fractures treated with circular external fixators had earlier weight-bearing and superior function compared with those managed with plate fixation.6

–A randomized controlled trial of patients with medial compartment knee osteoarthritis reported similar radiographic outcomes six years postoperatively among those who had opening-wedge high tibial osteotomy compared with those who had undergone closing-wedge high tibial osteotomy. The closing-wedge group had fewer complications but greater prevalence of conversion to total knee arthroplasty.

Foot and Ankle Reconstruction

–A multicenter prospective study comparing ankle arthroplasty with ankle arthrodesis noted similar patient-reported outcomes, although revision rates and major complications were higher following ankle replacement.

Managing Postoperative Complications

–A comparative study noted a lower prevalence of pin-site infections with the use of chlorhexidine (9.2%) compared with povidone-iodine (27.9%) following external fixation.7

–A randomized study revealed a 27% reduction in external fixation time with the use of low-intensity pulsed ultrasound for tibial osteoplasty.8

–A randomized trial in patients undergoing bilateral tibial lengthening showed no improvement in postoperative pain or ankle-joint mobility following botulinum toxin A injection in the calf muscle.9

New Tools and Techniques

–In a matched-pair study, patients undergoing femoral lengthening using a motorized intramedullary nail showed better consolidation indices, better knee mobility, and decreased complication rates compared with conventional external fixation.10

References

  1. MasquijoJJ, Lanfranchi L, Torres-Gomez A, Allende V. Guided growth with the tension band plate construct: a prospective comparison of 2 methods of implant placement. J Pediatr Orthop. 2015 Apr-May;35(3):e20
  2. Dwan K, Phillipi CA, Steiner RD, Basel D. Bisphosphonate therapy for osteogenesis imperfecta. Cochrane Database Syst Rev. 2014;7:CD005088. Epub 2014 Jul 23
  3. Hald JD, Evangelou E, Langdahl BL, Ralston SH. Bisphosphonates for the prevention of fractures in osteogenesis imperfecta: meta-analysis of placebo-controlled trials. J Bone Miner Res.2014 Nov 18
  4. Solfelt DA, Hill BW, Anderson CP, Cole PA. Supracondylar osteotomy for the treatment of cubitus varus in children: a systematic review. Bone Joint J. 2014May;96-B(5):691-700
  5. Rodrigues FL, de Abreu LC, Valenti VE, Valente AL, da Costa Pereira Cestari R,Pohl PH, Rodrigues LM. Bone tissue repair in patients with open diaphyseal tibial fracture treated with biplanar external fixation or reamed locked intramedullary nailing. Injury. 2014 Nov;45(Suppl 5):S32-5
  6. Fadel M, Ahmed MA, Al-Dars AM, Maabed MA, Shawki H. Ilizarov external fixation versus plate osteosynthesis in the management of extra-articular fractures of the distal tibia. Int Orthop. 2015 Mar;39(3):513-9. Epub 2014 Dec 5
  7. Cam R, Demir Korkmaz F, Oner Şavk S. Effects of two different solutions used in pin site care on the development of infection. Acta Orthop Traumatol Turc.2014;48(1):80-5
  8. Salem KH, Schmelz A. Low-intensity pulsed ultrasound shortens the treatment time in tibial distraction osteogenesis. Int Orthop. 2014 Jul;38(7):1477-82. Epub 2014 Jan 7
  9. Lee DH, Ryu KJ, Shin DE, Kim HW. Botulinum toxin A does not decrease calf pain or improve ROM during limb lengthening: a randomized trial. Clin Orthop Relat Res.2014 Dec;472(12):3835-41
  10. Horn J, Grimsrud Ø, Dagsgard AH, Huhnstock S, Steen H. Femoral lengthening with a motorized intramedullary nail. Acta Orthop. 2015 Apr;86(2):248-56. Epub 2014 Sep 5

JBJS Reviews Editor’s Choice–Bisphosphonate-Related Femoral Fractures

In December 1996, a group of investigators reported the results of the Fracture Intervention Trial, a randomized controlled trial that compared the effect of alendronate plus calcium or calcium supplementation alone on the risk of fractures in women who already had evidence of vertebral fractures. The results showed that in patients managed with alendronate, there was a 51% decrease in the risk of hip fractures, a 46% decrease in the risk of vertebral fractures, and a 44% decrease in the risk of distal radial fractures when compared with patients managed with calcium alone. These results, as well as those from several other reports, supported the regulatory approval of alendronate (marketed under the trade name Fosamax) for the treatment of postmenopausal osteoporosis in the United States and many countries abroad. Alendronate thus became the first drug in a class of compounds known as the nitrogen-containing bisphosphonates to demonstrate these beneficial effects.

Approximately a decade later, and after millions of patients had undergone treatment, some disturbing reports suggested a potential suppression of bone turnover in association with long-term alendronate therapy. Bone biopsies from selected patients suggested diminished kinetic indices of bone formation. This was believed to lead to increased susceptibility to fracture and delayed healing of nonspinal fractures such as fractures of the femoral shaft. Additional reports suggested the occurrence of insufficiency or low-energy fractures in patients who used alendronate for several years. While epidemiological findings suggested that these fractures are very rare even among women who have been managed with bisphosphonates for as long as a decade, the American Society for Bone and Mineral Research convened a task force to understand the pathophysiology of these atypical fractures and to gain further information on the association of these fractures with bisphosphonates. The term “atypical femoral fracture” was adopted to distinguish this type of fracture as a unique entity in order to avoid a suggestion that it is exclusively associated with bisphosphonate use.

Atypical femoral fractures can occur anywhere along the shaft of the femur from just distal to the lesser trochanter to just proximal to the supracondylar flare of the distal femoral metaphysis. They may be transverse or short-oblique in configuration, are typically noncomminuted or minimally comminuted, are associated with minimal or no trauma, and may be associated with a medial spike. Incomplete fractures may involve only the lateral cortex. Because these fractures occur as a result of brittle failure while most osteoporotic patients show some ductility with deformation prior to failure, atypical femoral fractures most likely occur through bone that has undergone alterations in its mechanical and material properties. This further supports the notion that these fractures are unique and distinct from typical osteoporotic fractures of the femur.

While current evidence suggests a strong relationship between the use of bisphosphonates and the genesis of atypical femoral fractures, we now know that denosumab, a drug that inhibits osteoclastogenesis but is unrelated to the bisphosphonates, also may be associated with these fractures. Moreover, some patients who have never taken bisphosphonates or denosumab have presented with what appear to be atypical femoral fractures. Thus, atypical femoral fractures are not exclusive to patients who use osteoclast-inhibiting drugs, and this presents a more complicated picture regarding the etiology of this unique type of fracture.

In the March 2015 issue of JBJS Reviews, Blood et al. summarize current thinking regarding the evaluation and treatment of atypical femoral fractures. The authors note that these fractures can be treated successfully with intramedullary nailing and discontinuation of bisphosphonate therapy. However, there is a potential for a delay in healing. Prodromal thigh pain and radiographic evidence of a radiolucent line in patients with a history of atypical femoral fracture or chronic bisphosphonate use are strong indicators of impending fracture. In these patients, prophylactic fixation should be considered. In addition, patients with prodromal thigh pain who are receiving chronic bisphosphonate therapy but do not have radiographic evidence of incomplete fracture require further workup and may benefit from magnetic resonance imaging. For patients who have incomplete fractures and no pain, the authors recommend a trial of conservative therapy, including protected weight-bearing, discontinuation of bisphosphonate therapy, and supplementation with calcium and vitamin D (800 to 1000 IU) per day. While no recommendation currently exists regarding the duration of bisphosphonate therapy, most experts recommend discontinuation after five years. Moreover, as bisphosphonates are not the only class of compounds that may be associated with these fractures, further information is needed in order to make informed decisions regarding the use of specific drugs and the duration of their use. While treatment of atypical femoral fractures with an anabolic therapy such as parathyroid hormone has been proposed, there are no definitive data to support this suggestion at this time.

The use of bisphosphonates and denosumab to treat osteoporosis represents a major step forward. However, it is possible that there are specific subsets of patients who are more sensitive to pharmacological suppression of bone remodeling and who may not be candidates for this kind of therapy. Further investigation is required to understand the safety of prolonged use of osteoclast-inhibiting drugs.

Thomas A. Einhorn, MD, Editor

Click here for another OrthoBuzz post about this JBJS Reviews article.

Preventing Atypical Femoral Fractures Related to Bisphosphonates

Physicians worldwide frequently prescribe bisphosphonates such as alendronate (Fosamax) and ibandronate (Boniva) to treat osteoporosis and prevent fragility fractures. Unfortunately, long-term bisphosphonate use has been linked to an increased risk of atypical femoral fractures. In the March 3, 2015 edition of JBJS Reviews, Blood et al. offer some guidance on how to prevent such fractures.

The authors note that prodromal thigh pain and a radiolucent line on X-rays of patients with a history of chronic bisphosphonate use are strong indicators of an impending fracture. Among bisphosphonate users who have an incomplete fracture with little or no pain, the authors recommend a trial of discontinued bisphosphonates, protected weight-bearing, calcium and vitamin-D supplementation, and possible teriparatide (Forteo) therapy. They add that prophylactic fixation should be considered if there is no radiographic or symptomatic improvement after two to three months of that conservative approach. Blood et al. further recommend that patients at high risk for atypical femoral fracture, should consider discontinuing bisphosphonate therapy after five years of continuous use. They also encourage orthopaedists to assess the contralateral femur for signs of impending fracture in patients who have already had an atypical femoral fracture.

The recommendations by Blood et al. notwithstanding, we should stress that the absolute risk of atypical femoral fractures fractures is low (3.2 to 50 cases per 100,000 person-years among short-term bisphosphonate users and about 100 cases per 100,000 person-years among long-term users). Consequently, for most people with osteoporosis, the proven fragility-fracture risk-reduction benefits of bisphosphonates outweigh the risks of atypical femoral fracture.

Readers interested in this subject may want to read a related Case Connections article, which springboards from a January 14, 2015 Case Connector article.

Another Look at Bisphosphonates and Jaw Osteonecrosis

A recent study in the Journal of Clinical Endocrinology & Metabolism found that approximately one out of 200 Taiwanese who used oral alendronate long term for osteoporosis developed osteonecrosis of the jaw (ONJ). In comparison, among a group treated with raloxifene for osteoporosis, only one out of 1,882 developed ONJ. Risk factors for developing ONJ among alendronate users included diabetes, RA, and exposure to the drug for more than three years.

Although this study reinforces an association between oral bisphosphonates and jaw osteonecrosis, it also demonstrates that this adverse effect is uncommon. While the incidence of ONJ in this study was 7 times higher with alendronate than with raloxifene, the incidence rate of ONJ attributed to alendronate use was only 283 per 100,000 persons per year. The increased relative risk with alendronate is worth noting, but the absolute risk remains low, and for people with osteoporosis, the fracture risk-reduction benefits of bisphosphonates continue to outweigh the risk of jaw osteonecrosis.