Injury | International Journal of the Care of the Injured - Volume 47 - Supplement 2

Fracture healing in osteoporotic bone

Wing Hoi Cheung

*, Theodore Miclau

, Simon Kwoon-Ho Chow

, Frank F. Yang

, Volker Alt

Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China

Department of Orthopaedic Surgery, University of California, San Francisco, Orthopaedic Trauma Institute, University of California, San Francisco/San Francisco General Hospital,

San Francisco, CA 94110, United States

Department of Trauma Surgery, Giessen University Hospital, Giessen-Marburg, Germany

A B S T R A C T

As the world population rises, osteoporotic fracture is an emerging global threat to the well-being of elderly

patients. The process of fracture healing by intramembranous ossification or/and endochondral ossification

involve many well-orchestrated events including the signaling, recruitment and differentiation of mesenchymal

stem cells (MSCs) during the early phase; formation of a hard callus and extracellular matrix, angiogenesis and

revascularization during the mid-phase; and finally callus remodeling at the late phase of fracture healing.

Through clinical and animal research, many of these factors are shown to be impaired in osteoporotic bone. Animal

studies related to post-menopausal estrogen deficient osteoporosis (type I) have shown healing to be prolonged

with decreased levels of MSCs and decreased levels of angiogenesis. Moreover, the expression of estrogen receptor

(ER) was shown to be delayed in ovariectomy-induced osteoporotic fracture. This might be related to the observed

difference in mechanical sensitivity between normal and osteoporotic bones, which requires further experiments

to elucidate.

In mice fracture models related to senile osteoporosis (type II), it was observed that chondrocyte and osteoblast

differentiation were impaired; and that transplantation of juvenile bone marrow would result in enhanced callus

formation. Other factors related to angiogenesis and vasculogenesis have also been noted to be impaired in aged

models, affecting the degradation of cartilaginous matrixes and vascular invasion; the result is changes in matrix

composition and growth factors concentrations that ultimately impairs healing during age-related osteoporosis.

Most osteoporotic related fractures occur at metaphyseal sites clinically, and reports have indicated that

differences exist between diaphyseal andmetaphyseal fractures. An animal model that satisfies three main criteria

(metaphyseal region, plate fixation, osteoporosis) is suggested for future research for more comprehensive

understanding of the impairment in osteoporotic fractures. Therefore, a metaphyseal fracture or osteotomy that

achieves complete discontinuity fixed with metal implants is suggested on ovariectomized aged rodent models.

K E Y W O R D S

Fracture healing

Osteoporotic bone

Aging

Metaphyseal fracture

Estrogen receptor

Introduction

Bone tissues demonstrate a remarkable ability to regenerate

following fracture injury, recovering from structural failure and lost

physiological function [1]. The cascade of events following traumatic

bone injury is well-documented in both stabilized and non-stabilized

fractures. The former primarily heal via intramembranous ossification

in which bone regenerates directly from mesenchymal cells, while the

latter primarily heal via endochondral ossification in which bone

regenerates through a cartilage intermediate [1

–

5]. Both events begin

with the formation of a hematoma between the damaged bone ends

and surrounding soft tissues. Inflammatory cells are recruited by local

chemokines to debride the wound, which allows for the migration of

mesenchymal stem cells. In stabilized fractures, these cells differen-

tiate directly into osteoblasts and form trabecular bone [5]. In non-

stabilized fractures, these cells alter their fate and differentiate into

granulation and cartilage tissues [1]. A predominantly cartilaginous

soft fracture callus develops and stabilizes the injury site. Then, a hard

fracture callus develops through vascularization and mineralization of

the extracellular matrix, which yield trabecular bone. Once trabecular

bone is generated in both ossification processes, a series of bone

depositions and resorptions by osteoblasts and osteoclasts, respect-

ively, reform lamellar bone.

Despite the fine degree of orchestration during fracture healing, the

process may be impaired. Currently, 10

–

15% of the approximately 15

million fractures that occur annually result in poor or unresolved

Corresponding author at: Department of Orthopaedics and Traumatology, The Chinese

University of Hong Kong. 5/F LCW Clinical Sciences Building, Prince of Wales Hospital, Shatin,

Hong Kong, People

’

s Republic of China. Tel.: +852 2632 1559; fax: +852 2632 4618.

E-mail address

louis@ort.cuhk.edu.hk

(W.H. Cheung).

Injury, Int. J. Care Injured 47S2 (2016) S21

–

S26

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