Effect of intermittent parathyroid hormone (1–34) treatment on the bone response after placement of titanium implants into the tibia of ovariectomized rats

First Department of Oral and Maxillofacial Surgery, School of Dentistry, Showa University, Tokyo, Japan.
Journal of Oral and Maxillofacial Surgery (Impact Factor: 1.43). 05/2003; 61(4):471-80. DOI: 10.1053/joms.2003.50093
Source: PubMed


This study investigated the effect of parathyroid hormone (1-34) [PTH(1-34)] on bone reactions after tibial placement of titanium screw implants into ovariectomized rats.
Twelve-week-old female Wistar rats were divided into 3 groups of 24. The first group (Sham group) was sham-operated; the second group (OVX group) was ovariectomized only; and the third group (PTH group) was subcutaneously administered 30 microg/kg PTH in the dorsal region 3 days per week starting the fourth week after ovariectomy until the end of the experiment. Titanium screw implants were placed in the proximal metaphysis of the tibia of all 3 groups at 168 days after surgery. The animals were killed 7, 14, 28, and 56 days after implantation. Undecalcified sections were prepared and evaluated by light microscopy. Histomorphometric measurements were obtained using a computer-based image analyzer to quantify the unit bone mass around the implant and the rate of implant-bone contact.
When PTH administration was started 21 days after ovariectomy, the volume density of bone around implants in the PTH group was almost the same as that of the Sham group throughout the entire observation period. This finding suggests that not only can intermittent human PTH(1-34) administration prevent resorption of newly generated trabeculae around an implant but also it can aid in the recovery of bone volume lost due to ovariectomy.
When dental implants are applied to jaw bone showing trabecular bone loss, it may be possible to increase bone density around an implant by intermittent human PTH(1-34) administration and thereby improve clinical results.

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    • "Experimental distraction osteogenesis (Seebach et al. 2004, Aleksyniene et al. 2006, 2009) and fracture healing show increased callus volume and mechanical strength (Kim et al. 1996, Andreassen et al. 1999, Alkhiary et al. 2005, Manabe et al. 2007, Barnes et al. 2008, Nozaka et al. 2008, Aspenberg et al. 2009). Until now, research on fixation of prostheses by adjuvant PTH administration has been confined to experimental rodent settings with pathological low bone density (Shirota et al. 2003, Gabet et al. 2006) or involving transcortical screw insertion (Skripitz et al. 2000b, Skripitz and Aspenberg 2001b). "
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    ABSTRACT: Intermittent administration of parathyroid hormone (PTH) has an anabolic effect on bone, as confirmed in human osteoporosis studies, distraction osteogenesis, and fracture healing. PTH in rat models leads to improved fixation of implants in low-density bone or screw insertion transcortically. We examined the effect of human PTH (1-34) on the cancellous osseointegration of unloaded implants inserted press-fit in intact bone of higher animal species. 20 dogs were randomized to treatment with human PTH (1-34), 5 μg/kg/day subcutaneously, or placebo for 4 weeks starting on the day after insertion of a cylindrical porous coated plasma-sprayed titanium alloy implant in the proximal metaphyseal cancellous bone of tibia. Osseointegration was evaluated by histomorphometry and fixation by push-out test to failure. Surface fraction of woven bone at the implant interface was statistically significantly higher in the PTH group by 1.4 fold with (median (interquartile range) 15% (13-18)) in the PTH group and 11% (7-13) in control. The fraction of lamellar bone was unaltered. No significant difference in bone or fibrous tissue was observed in the circumferential regions of 0-500, 500-1,000, and 1,000-2,000 μm around the implant. Mechanically, the implants treated with PTH showed no significant differences in total energy absorption, maximum shear stiffness, or maximum shear strength. Intermittent treatment with PTH (1-34) improved histological osseointegration of a prosthesis inserted press-fit at surgery in cancellous bone, with no additional improvement of the initial mechanical fixation at this time point.
    Acta Orthopaedica 08/2012; 83(4):411-9. DOI:10.3109/17453674.2012.702388 · 2.77 Impact Factor
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    • "This deficit can be reversed by systemic administration of insulin or parathyroid hormone (PTH)-related protein (PTHrP), an important modulator of bone formation and bone remodelling [14] [15]. Moreover, this type of administration of PTH or PTHrP was shown to promote bone repair in ovariectomized rats [16] [17] [18] or rabbits with glucocorticoid-related osteopenia [19], respectively. Furthermore, it was recently shown that every other day injection of PTHrP (1–36) or PTHrP (107–139) was similarly efficient in improving the delayed regeneration of marrow-ablated mouse tibia in mice with glucocorticoid-or diabetic-related osteopenia [14] [20] [21]. "
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    ABSTRACT: Parathyroid hormone-related protein (PTHrP) is an important modulator of bone formation. Recently, we reported that PTHrP (107-111) (osteostatin) coating onto mesoporous ceramics confers osteogenic activity to these materials. Bone repair is dramatically compromised in osteopenia/osteoporosis. Thus, we examined the efficacy of unmodified and organically modified SBA15 ceramics loaded with osteostatin in promoting bone repair in an osteoporotic rabbit model. Osteoporosis was induced in New Zealand rabbits by methylprednisolone administration, and healthy rabbits were used as controls. Tested materials were implanted into a femoral cavitary defect, and animals were sacrificed at 2 weeks post-implantation. At this time, implants were encapsulated by a variable layer of fibrotic tissue with no evidence of inflammation. Similarly to observations in normal rabbits, both types of osteostatin-loaded bioceramics induced tissue regeneration associated with increased staining for PCNA, Runx2, osteopontin, and/or vascular endothelial growth factor in osteoporotic rabbits. Our present findings demonstrate that these osteostatin-bearing bioceramics increase the early repair response not only in normal bone but also in osteoporotic bone after a local injury.
    Acta biomaterialia 03/2012; 8(6):2317-23. DOI:10.1016/j.actbio.2012.03.014 · 6.03 Impact Factor
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    • "Intermittent systemic administration of 1-34 PTH peptide can enhance osseointegration of titanium implants in a rat model (Shirota et al., 2003; Mair et al., 2009). This treatment can also increase bone regeneration at different anatomic sites (Andreassen et al., 1999). "
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    ABSTRACT: Teriparatide is an anabolic osteoporosis therapeutic agent that can improve healing after fractures and periodontal surgeries. Clinical studies investigating the effects of teriparatide on the osseointegration of titanium implants have not been performed. We conducted an open-label randomized controlled feasibility study and included 24 individuals with edentulous lower jaws. The participants received 2 study implants in the mandible during interforaminal dental implant surgery. They were randomly assigned to receive either 20 µg of teriparatide once daily for 28 days or no treatment. Study implants were retrieved from 23 participants after 9 weeks and were subjected to histomorphometric analyses. Endpoints were new bone-volume-per-tissue-volume (NBV/TV) and new bone-to-implant-contact (NBIC). We report here that median values of NBV/TV in the control and the teriparatide groups were 15.4% vs. 17.6% in the periosteal compartment, 11.3% vs. 16.5% in the cortical compartment, and 7.3% vs. 12.0% in the medullary compartment, respectively. NBIC median values in the control and the teriparatide groups were 3.3% vs. 4.1% in the periosteal compartment, 5.0% vs. 4.4% in the cortical compartment, and 0.3% vs. 1.4% in the medullary compartment, respectively. The results provide the first histological data on the osseointegration of titanium study implants in individuals treated with teriparatide. number, NCT00089674.
    Journal of dental research 05/2011; 90(8):1001-6. DOI:10.1177/0022034511407920 · 4.14 Impact Factor
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