Highlights
- •A number of factors can influence the incidence of delayed union or non-union after fracture.
- •Increased age appears to be a risk factor for delayed union or non-union.
- •The use of non-steroidal anti-inflammatory drugs and smoking put the patient at greatest risk of these complications.
- •Therapies such as ultrasound can minimize the risk of delayed union or non-union.
Abstract
Older patients are commonly at a higher risk of experiencing a bone fracture. Complications
during fracture healing, including delayed union and non-union, can arise as a result
of a multitude of patient and treatment factors.
This review describes those factors which contribute to a greater risk of delayed
union and non-union with particular reference to the elderly population and discusses
therapies that may enhance the fracture healing process in the hope of reducing the
incidence of delayed union and non-union.
Increasing age does seem to increase the risk of delayed union or non-union. In addition,
smoking and the treatment of post-fracture pain with non-steroidal anti-inflammatory
drugs (NSAIDs) put the patient at the greatest risk, while ultrasound therapy appears
to be a non-invasive, effective treatment option to reduce the risk of delayed union
or non-union. The use of growth factors and of stem cells and the role of surgery
are also discussed.
Keywords
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References
- Symptomatic fracture incidence in elderly men and women: the dubbo osteoporosis epidemiology study.Osteoporos. Int. 1994; 4: 277-282
- The biology of fracture healing in long bones.J. Bone Jt. Surg. [Br]. 1978; 60: 150-162
- The biology of fracture healing.Injury. 2011; 42: 551-555
- The biology of fracture healing: an overview for clinicians. Part I.Clin. Orthop. Relat. Res. 1989; 248: 283-293
- Prevalence of long-bone non-unions.Injury. 2007; 38: S3-9
- Delayed unions of the tibia.J. Bone Jt. Surg. Am. 2006; 88: 205-216
- Tibia shaft fractures: costly burden of nonunions.BMC Musculoskelet. Disord. 2013; 14: 1
- Management of complex tibial and femoral nonunion using the Ilizarov technique, and its cost implications.Bone Jt. J. 2006; 88: 928-932
- Fracture healing in the elderly patient.Exp. Gerontol. 2006; 41: 1080-1093
- Functional recovery following hip fracture in the elderly.J. Orthop. Trauma. 1997; 11: 594-599
- Cellular basis for age‐related changes in fracture repair.J. Orthop. Res. 2005; 23: 1300-1307
- The influence of osteoporosis in femoral fracture healing time.Injury. 2009; 40: 663-668
- Monitoring and healing analysis of 100 tibial shaft fractures.Langenbeck's Arch. Surg. 2002; 387: 146-152
- Estimating the risk of nonunion following nonoperative treatment of a clavicular fracture.J. Bone Jt. Surg. Am. 2004; 86: 1359-1365
- Incidence of fracture-healing complications after femoral neck fractures.Clin. Orthop. Relat. Res. 2007; 458: 175-179
- Predictors of outcome of floating knee injuries in adults: 89 patients followed for 2–12 years.Acta Orthop. Scand. 2001; 72: 385-394
- Influence of age on mechanical properties of healing fractures and intact bones in rats.Acta Orthop. Scand. 1982; 53: 527-534
- The effect of aging on fracture healing in the rat.Calcif. Tissue Int. 1989; 45: 292-297
- Influence of age and mechanical stability on bone defect healing: age reverses mechanical effects.Bone. 2008; 42: 758-764
- Patient-related risk factors for fracture-healing complications in the United Kingdom general practice research database.Acta Orthop. 2012; 83: 653-660
- Intrinsic and extrinsic risk factors for nonunion after nonoperative treatment of midshaft clavicle fractures.Orthop. Traumatol.: Surg. Res. 2015; 101: 197-200
- Ankle fusion in a high risk population: an assessment of nonunion risk factors.Foot Ankle Int. 1999; 20: 491-496
- Cigarette smoking delays bone healing a prospective study of 200 patients operated on by the hemicallotasis technique.Acta Orthop. Scand. 2004; 75: 347-351
- The effect of transdermal nicotine on fracture healing in a rabbit model.J. Orthop. Trauma. 2012; 26: 724-727
- Tobacco extract but not nicotine impairs the mechanical strength of fracture healing in rats.J. Orthop. Res. 2006; 24: 1472-1479
- The rate of pseudarthrosis (surgical nonunion) in patients who are smokers and patients who are nonsmokers: a comparison study.Spine. 1986; 11: 942-943
- Effect of smoking on tibial shaft fracture healing.Clin. Orthop. Relat. Res. 1999; 365: 184-200
- Can a combination of different risk factors be correlated with leg fracture healing time?.J. Orthop. Traumatol. 2013; 14: 51-57
- Ankle fusion in a high risk population: an assessment of nonunion risk factors.Foot Ankle Int. 1999; 20: 491-496
- Nonsteroidal anti-inflammatory drugs’ impact on nonunion and infection rates in long-bone fractures.J. Trauma Acute Care Surg. 2014; 76: 779-783
- Cigarette smoking and open tibial fractures.Injury. 2001; 32: 61-65
- Acceleration of tibia and distal radius fracture healing in patients who smoke.Clin. Orthop. Relat. Res. 1997; 337: 198-207
- Are smokers a risk group for delayed healing of tibial shaft fractures?.Ann. Chir. Gynaecol. 1992; 82: 254-262
- Diabetes and its effect on bone and fracture healing.Curr. Osteoporos. Rep. 2015; 13: 327-335
- Perioperative complications of lumbar instrumentation and fusion in patients with diabetes mellitus.Spine J. 2003; 3: 496-501
- The influence of diabetes mellitus on the healing of closed fractures.Clin. Orthop. Relat. Res. 1988; 232: 210-216
- Ankle fractures in patients with diabetes mellitus.Bone Jt. J. 2005; 87: 489-495
- Outcomes of ankle fractures in patients with uncomplicated versus complicated diabetes.Foot Ankle Int. 2011; 32: 120-130
- Complications of ankle fracture in patients with diabetes.J. Am. Acad. Orthop. Surg. 2008; 16: 159-170
- Cyclo-oxygenase 2 function is essential for bone fracture healing.J. Bone Miner. Res. 2002; 17: 963-976
- Pharmacological agents and impairment of fracture healing: what is the evidence?.Injury. 2008; 39: 384-394
- Effect of nonsteroidal antiinflammatory drugs on fracture healing: a laboratory study in rats.J. Orthop. Trauma. 1995; 9: 392-400
- Differential inhibition of fracture healing by non-selective and cyclooxygenase-2 selective non-steroidal anti-inflammatory drugs.J. Orthop. Res. 2003; 21: 670-675
- Influence of diclofenac (group of nonsteroidal anti-inflammatory drugs) on fracture healing.Arch. Orthop. Trauma Surg. 2003; 123: 327-332
- COX-2 selective NSAID decreases bone ingrowth in vivo.J. Orthop. Res. 2002; 20: 1164-1169
- Nonsteroidal anti-inflammatory drugs delay tibial fracture union.Injury. 1996; 27: 375
- Patient-related risk factors for fracture-healing complications in the United Kingdom general practice research database.Acta Orthop. 2012; 83: 653-660
- Use of oral corticosteroids and risk of fractures.J. Bone Miner. Res. 2000; 15: 993-1000
- Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone.J. Clin. Investig. 1998; 102: 274
- Effect of cortisone on experimental fractures in the rabbit.Exp. Biol. Med. 1950; 73: 678-681
- Systemic corticosteroids inhibit bone healing in a rabbit ulnar osteotomy model.Acta Orthop. Scand. 2000; 71: 316-321
- Effects of short-term treatment with corticosteroids and indomethacin on bone healing: a mechanical study of osteotomies in rats.Acta Orthop. Scand. 1992; 63: 607-611
- Failure of cortisone to delay or to prevent the healing of fractures in rats.J. Bone Joint Surg. Am. 1952; 34: 665-677
- Effects of short-term treatment with systemic prednisone on bone healing: an experimental study in rats.Dent. Traumatol. 2005; 21: 222-225
- Suppressed bone turnover by bisphosphonates increases microdamage accumulation and reduces some biomechanical properties in dog rib.J. Bone Miner. Res. 2000; 15: 613-620
- Nonoperative versus prophylactic treatment of bisphosphonate-associated femoral stress fractures.Clin. Orthop. Relat. Res. 2011; 469: 2028-2034
- Zoledronic acid and clinical fractures and mortality after hip fracture.N. Engl. J. Med. 2007; 357: 1799-1809
- The relation between bisphosphonate use and non-union of fractures of the humerus in older adults.Osteoporos. Int. 2009; 20: 895-901
- Bisphosphonates and their influence on fracture healing: a systematic review.Osteoporos. Int. 2015; 26: 1251-1260
- The effect of anticoagulant therapy on bone repair.J. Bone Joint Surg. Am. 1956; 38: 270-282
- The effect of various types low molecular weight heparins on fracture healing.Thromb. Res. 2013; 131: e114-9
- The effect of Low molecular weight heparins on fracture healing.Open Orthop. J. 2015; 9: 226
- Enoxaparin and rivaroxaban have different effects on human mesenchymal stromal cells in the early stages of bone healing.Bone Jt. Res. 2016; 5: 95-100
- Rivaroxaban does not impair fracture healing in a rat femur fracture model: an experimental study.BMC Musculoskelet Disord. 2015; 16: 1
- Mode & mechanism of low intensity pulsed ultrasound (LIPUS) in fracture repair.Ultrason. 2016; 70: 45-52
- Ultrasound treatment for accelerating fracture healing of the distal radius: a control study.Acta Cir. Bras. 2014; 29: 765-770
- The use of low-intensity ultrasound to accelerate the healing of fractures.J. Bone Jt. Surg. Am. 2001; 83: 259-
- Recombinant human bone morphogenetic protein-2 in the treatment of bone fractures.Biologics. 2008; 2: 345-354
- Recombinant human bone morphogenetic protein-2 for treatment of open tibial fractures.J. Bone Jt. Surg. 2002; 84: 2123-2134
- Recombinant human BMP-2 for the treatment of open tibial fractures.Orthopedics. 2012; 35: e847-54
- A health economic analysis of the use of rhBMP-2 in Gustilo–Anderson grade III open tibial fractures for the UK, Germany and France.Injury. 2009; 40: 1269-1275
- Teriparatide in the treatment of non-unions: scientific and clinical evidences.Injury. 2013; 44: S54-7
- Teriparatide improves fracture healing and early functional recovery in treatment of osteoporotic intertrochanteric fractures.Medicine. 2016; 95: e3626
- Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis.Lancet. 2007; 370: 657-666
- Calcium plus vitamin D supplementation and the risk of fractures.N. Engl. J. Med. 2006; 354: 669-683
- The effect of calcium and vitamin D3 supplementation on the healing of the proximal humerus fracture: a randomized placebo-controlled study.Calcif. Tissue Int. 2004; 75: 183-188
- concentration in patients with normal and impaired bone union.Pol. Orthop. Traumatol. 2012; 78: 1-3
- Surgical treatment of nonarticular distal tibia fractures.J. Am. Acad. Orthop. Surg. 2006; 14: 406-416
- Percutaneous autologous bone-marrow grafting for nonunions.J. Bone Joint Surg. Am. 2005; 87: 1430-1437
- Autologous marrow injection as a substitute for operative grafting of tibial nonunions.Clin. Orthop. Relat. Res. 1991; 266: 259-270
- Bone fracture healing: cell therapy in delayed unions and nonunions.Bone. 2015; 70: 93-101
- Vascular endothelial growth factor gene-activated matrix (VEGF165-GAM) enhances osteogenesis and angiogenesis in large segmental bone defects.J. Bone Miner. Res. 2005; 20: 2028-2035
- Vascular endothelial growth factor: an essential component of angiogenesis and fracture healing.HSS J. 2010; 6: 85-94
- Acceleration of fracture healing in nonhuman primates by fibroblast growth factor-2.J. Clin. Endocrinol. Metab. 2001; 86: 875-880
- Local application of growth factors (insulin-like growth factor-1 and transforming growth factor-β1) from a biodegradable poly (d, l-lactide) coating of osteosynthetic implants accelerates fracture healing in rats.Bone. 2001; 28: 341-350
Article info
Publication history
Published online: July 21, 2016
Accepted:
July 20,
2016
Received in revised form:
July 19,
2016
Received:
July 12,
2016
Identification
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© 2016 Elsevier Ireland Ltd. All rights reserved.
