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Intermittent Administration of Parathyroid Hormone [1-34] Prevents Particle-Induced Periprosthetic Osteolysis in a Rat Model.

Bi F, Shi Z, Zhou C, Liu A, Shen Y, Yan S - PLoS ONE (2015)

Bottom Line: Administration of PTH[1-34] significantly increased the bone mineral density of the distal femur, BV/TV, Tb.N, Tb.Th, Tb.Sp, Con.D, SMI, and maximal fixation strength in the PTH group compared to that in the control group.SEM revealed higher bone-implant contact, thicker lamellar bone, and larger trabecular bone area in the PTH group than in the control group.A higher mineral apposition rate was observed in the PTH group compared to both the blank and control groups.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopedic Surgery, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

ABSTRACT
We examined whether intermittent administration of parathyroid hormone [1-34] (PTH[1-34]; 60 μg/kg/day) can prevent the negative effects of titanium (Ti) particles on implant fixation and periprosthetic osteolysis in a rat model. Eighteen adult male rats (12 weeks old, bones still growing) received intramedullary Ti implants in their bilateral femurs; 6 rats from the blank group received vehicle injections, and 12 rats from the control group and PTH treatment group received Ti particle injections at the time of operation and intra-articular injections 2 and 4 weeks postoperatively. Six of the rats that received Ti particles from the PTH group also received PTH[1-34] treatment. Six weeks postoperatively, all specimens were collected for assessment by X-ray, micro-CT, biomechanical, scanning electron microscopy (SEM), and dynamic histomorphometry. A lower BMD, BV/TV, Tb.N, maximal fixation strength, and mineral apposition rate were observed in the control group compared to the blank group, demonstrating that a periprosthetic osteolysis model had been successfully established. Administration of PTH[1-34] significantly increased the bone mineral density of the distal femur, BV/TV, Tb.N, Tb.Th, Tb.Sp, Con.D, SMI, and maximal fixation strength in the PTH group compared to that in the control group. SEM revealed higher bone-implant contact, thicker lamellar bone, and larger trabecular bone area in the PTH group than in the control group. A higher mineral apposition rate was observed in the PTH group compared to both the blank and control groups. These findings imply that intermittent administration of PTH[1-34] prevents periprosthetic osteolysis by promoting bone formation. The effects of PTH[1-34] were evaluated at a suprapharmacological dosage to the human equivalent in rats; therefore, additional studies are required to demonstrate its therapeutic potential in periprosthetic osteolysis.

No MeSH data available.


Related in: MedlinePlus

SEM image from the blank group used to illustrate how the histomorphometric analysis was performed.(A) Bone–implant contact: the length of contact area (red line)/perimeter of the implant; (B) thickness of lamellar bone (red arrows) around the implant; and (C) trabecular area in the SEM visual field (red area).
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pone.0139793.g004: SEM image from the blank group used to illustrate how the histomorphometric analysis was performed.(A) Bone–implant contact: the length of contact area (red line)/perimeter of the implant; (B) thickness of lamellar bone (red arrows) around the implant; and (C) trabecular area in the SEM visual field (red area).

Mentions: Bone morphogenesis around the implants was examined to assess potential bone formation following PTH[1–34] treatment. The specimens containing implants were embedded in resin for sectioning (n = 6 per group from different rats). Sections (50 μm thickness) were cut perpendicularly to the longitudinal axis of the implants using a saw microtome (Leica-SP1600, Leica Biosystems, Nussloch, Germany). Scanning electron microscope (SEM, TM–1000, Japan) images of the sections were used to assess bone–implant contact, thickness of lamellar bone around the implant, and trabecular area in the SEM visual field (Fig 4A–4C). The labeled bone surface and interlabeled thickness were detected by fluorescence microscopy (Leica DM5 500B, Leica Microsystems, Bensheim, Germany) and using Image-Pro Plus 6.0 software (IPP 6.0, Media Cybernetics Inc., Rockville, MD, USA). The data were used to calculate mineral apposition rate as follows: mineral apposition rate = interlabeled thickness per 10 days (expressed as μm/day). Then the sections were stained with a tartrate-resistant acid phosphatase (TRAP) staining kit following the manufacturer’s protocol (Sangon Biotech, Shanghai, CHN) to investigate changes at the cellular level.


Intermittent Administration of Parathyroid Hormone [1-34] Prevents Particle-Induced Periprosthetic Osteolysis in a Rat Model.

Bi F, Shi Z, Zhou C, Liu A, Shen Y, Yan S - PLoS ONE (2015)

SEM image from the blank group used to illustrate how the histomorphometric analysis was performed.(A) Bone–implant contact: the length of contact area (red line)/perimeter of the implant; (B) thickness of lamellar bone (red arrows) around the implant; and (C) trabecular area in the SEM visual field (red area).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4595472&req=5

pone.0139793.g004: SEM image from the blank group used to illustrate how the histomorphometric analysis was performed.(A) Bone–implant contact: the length of contact area (red line)/perimeter of the implant; (B) thickness of lamellar bone (red arrows) around the implant; and (C) trabecular area in the SEM visual field (red area).
Mentions: Bone morphogenesis around the implants was examined to assess potential bone formation following PTH[1–34] treatment. The specimens containing implants were embedded in resin for sectioning (n = 6 per group from different rats). Sections (50 μm thickness) were cut perpendicularly to the longitudinal axis of the implants using a saw microtome (Leica-SP1600, Leica Biosystems, Nussloch, Germany). Scanning electron microscope (SEM, TM–1000, Japan) images of the sections were used to assess bone–implant contact, thickness of lamellar bone around the implant, and trabecular area in the SEM visual field (Fig 4A–4C). The labeled bone surface and interlabeled thickness were detected by fluorescence microscopy (Leica DM5 500B, Leica Microsystems, Bensheim, Germany) and using Image-Pro Plus 6.0 software (IPP 6.0, Media Cybernetics Inc., Rockville, MD, USA). The data were used to calculate mineral apposition rate as follows: mineral apposition rate = interlabeled thickness per 10 days (expressed as μm/day). Then the sections were stained with a tartrate-resistant acid phosphatase (TRAP) staining kit following the manufacturer’s protocol (Sangon Biotech, Shanghai, CHN) to investigate changes at the cellular level.

Bottom Line: Administration of PTH[1-34] significantly increased the bone mineral density of the distal femur, BV/TV, Tb.N, Tb.Th, Tb.Sp, Con.D, SMI, and maximal fixation strength in the PTH group compared to that in the control group.SEM revealed higher bone-implant contact, thicker lamellar bone, and larger trabecular bone area in the PTH group than in the control group.A higher mineral apposition rate was observed in the PTH group compared to both the blank and control groups.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopedic Surgery, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

ABSTRACT
We examined whether intermittent administration of parathyroid hormone [1-34] (PTH[1-34]; 60 μg/kg/day) can prevent the negative effects of titanium (Ti) particles on implant fixation and periprosthetic osteolysis in a rat model. Eighteen adult male rats (12 weeks old, bones still growing) received intramedullary Ti implants in their bilateral femurs; 6 rats from the blank group received vehicle injections, and 12 rats from the control group and PTH treatment group received Ti particle injections at the time of operation and intra-articular injections 2 and 4 weeks postoperatively. Six of the rats that received Ti particles from the PTH group also received PTH[1-34] treatment. Six weeks postoperatively, all specimens were collected for assessment by X-ray, micro-CT, biomechanical, scanning electron microscopy (SEM), and dynamic histomorphometry. A lower BMD, BV/TV, Tb.N, maximal fixation strength, and mineral apposition rate were observed in the control group compared to the blank group, demonstrating that a periprosthetic osteolysis model had been successfully established. Administration of PTH[1-34] significantly increased the bone mineral density of the distal femur, BV/TV, Tb.N, Tb.Th, Tb.Sp, Con.D, SMI, and maximal fixation strength in the PTH group compared to that in the control group. SEM revealed higher bone-implant contact, thicker lamellar bone, and larger trabecular bone area in the PTH group than in the control group. A higher mineral apposition rate was observed in the PTH group compared to both the blank and control groups. These findings imply that intermittent administration of PTH[1-34] prevents periprosthetic osteolysis by promoting bone formation. The effects of PTH[1-34] were evaluated at a suprapharmacological dosage to the human equivalent in rats; therefore, additional studies are required to demonstrate its therapeutic potential in periprosthetic osteolysis.

No MeSH data available.


Related in: MedlinePlus