TY - JOUR
T1 - Endogenous tissue engineering
T2 - PTH therapy for skeletal repair
AU - Takahata, Masahiko
AU - Awad, Hani A.
AU - O'Keefe, Regis J.
AU - Bukata, Susan V.
AU - Schwarz, Edward M.
N1 - Funding Information:
This work was funded in part by grants from the Aircast Foundation and grants from the National Institutes of Health (AR056696, AR054041, DE019902). M.Takahata.H.A.Awad.R.J.O’Keefe.S.V.Bukata. E. M. Schwarz (*) The Center for Musculoskeletal Research, University of Rochester, 665, 601 Elmwood Avenue, Rochester NY 14642, USA e-mail: [email protected]
PY - 2012/3
Y1 - 2012/3
N2 - Based on its proven anabolic effects on bone in osteoporosis patients, recombinant parathyroid hormone (PTH 1-34) has been evaluated as a potential therapy for skeletal repair. In animals, the effect of PTH 1-34 has been investigated in various skeletal repair models such as fractures, allografting, spinal arthrodesis and distraction osteogenesis. These studies have demonstrated that intermittent PTH 1-34 treatment enhances and accelerates the skeletal repair process via a number of mechanisms, which include effects on mesenchymal stem cells, angiogenesis, chondrogenesis, bone formation and resorption. Furthermore, PTH 1-34 has been shown to enhance bone repair in challenged animal models of aging, inflammatory arthritis and glucocorticoid-induced bone loss. This pre-clinical success has led to off-label clinical use and a number of case reports documenting PTH 1-34 treatment of delayed-unions and non-unions have been published. Although a recently completed phase 2 clinical trial of PTH 1-34treatment of patients with radius fracture has failed to achieve its primary outcome, largely because of effective healing in the placebo group, several secondary outcomes are statistically significant, highlighting important issues concerning the appropriate patient population for PTH 1-34therapy in skeletal repair. Here, we review our current knowledge of the effects of PTH 1-34 therapy for bone healing, enumerate several critical unresolved issues (e.g., appropriate dosing regimen and indications) and discuss the long-term potential of this drug as an adjuvant for endogenous tissue engineering.
AB - Based on its proven anabolic effects on bone in osteoporosis patients, recombinant parathyroid hormone (PTH 1-34) has been evaluated as a potential therapy for skeletal repair. In animals, the effect of PTH 1-34 has been investigated in various skeletal repair models such as fractures, allografting, spinal arthrodesis and distraction osteogenesis. These studies have demonstrated that intermittent PTH 1-34 treatment enhances and accelerates the skeletal repair process via a number of mechanisms, which include effects on mesenchymal stem cells, angiogenesis, chondrogenesis, bone formation and resorption. Furthermore, PTH 1-34 has been shown to enhance bone repair in challenged animal models of aging, inflammatory arthritis and glucocorticoid-induced bone loss. This pre-clinical success has led to off-label clinical use and a number of case reports documenting PTH 1-34 treatment of delayed-unions and non-unions have been published. Although a recently completed phase 2 clinical trial of PTH 1-34treatment of patients with radius fracture has failed to achieve its primary outcome, largely because of effective healing in the placebo group, several secondary outcomes are statistically significant, highlighting important issues concerning the appropriate patient population for PTH 1-34therapy in skeletal repair. Here, we review our current knowledge of the effects of PTH 1-34 therapy for bone healing, enumerate several critical unresolved issues (e.g., appropriate dosing regimen and indications) and discuss the long-term potential of this drug as an adjuvant for endogenous tissue engineering.
KW - Allograft
KW - Fracture insufficiency
KW - Parathyroid hormone (PTH)
KW - Skeletal repair
UR - http://www.scopus.com/inward/record.url?scp=84859430471&partnerID=8YFLogxK
U2 - 10.1007/s00441-011-1188-4
DO - 10.1007/s00441-011-1188-4
M3 - Review article
C2 - 21626290
AN - SCOPUS:84859430471
SN - 0302-766X
VL - 347
SP - 545
EP - 552
JO - Cell and Tissue Research
JF - Cell and Tissue Research
IS - 3
ER -