Histomorphometric Evaluation of the Effects of Ovariectomy on Bone Turnover in Rat Caudal Vertebrae

Miyakoshi, Naohisa; Satô, Kôzô; Abe, Tomoki; Tsuchida, Tsunehisa; Tamura, Yasuki; Kudo, Takuya

doi:10.1007/s002239900626

Cited by 25 publications

(16 citation statements)

References 18 publications

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“…In contrast to the results from lumbar vertebrae, trabecular architecture in caudal vertebrae did not change in response to OVX and ZOL. Our results concur with previous reports on nonresponsiveness to OVX in caudal vertebrae [11,[15][16][17]. It has been suggested that differences in marrow composition between lumbar and caudal vertebrae play a role in responsiveness to OVX [11].…”

Section: Discussionsupporting

confidence: 92%

Influence of Early and Late Zoledronic Acid Administration on Vertebral Structure and Strength in Ovariectomized Rats

2008

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An annual infusion of zoledronic acid (ZOL) reduces fracture risk in osteoporotic patients. Previously, we showed that a single ZOL injection inhibited changes in bone microstructure and strength in rat tibiae after ovariectomy. Here, we determined the effects of a single ZOL injection as preventive and restorative treatment on the bone microstructure and strength in lumbar and caudal vertebrae of ovariectomized (OVX) rats. Twenty-nine female 35-weekold Wistar rats were divided into four groups: SHAM-OVX (n = 9), OVX (n = 5), OVX and early ZOL (n = 8), and OVX and late ZOL (n = 7). ZOL was given once (20 lg/kg body weight s.c.) at OVX in the early ZOL group and 8 weeks later in the late ZOL group; rats were killed 16 weeks after OVX. Trabecular and cortical bone microarchitecture were measured in lumbar (L3) and caudal (Cd6) vertebrae using micro-computed tomography, and compressive mechanical properties were determined in L3 vertebrae. Compared to SHAM-OVX, OVX rats had significantly lower BV/TV; SMI, Tb.N, Tb.Sp, and Conn.D tended to be deteriorated in lumbar vertebrae, while both ZOL groups did not differ from the SHAM-OVX group. Both ZOL groups had significantly higher BV/TV than OVX; the early ZOL group also had significantly lower SMI and higher Tb.Th. OVX tended to decrease mechanical properties, while early and late ZOL treatment inhibited OVX-induced degeneration. Neither OVX nor ZOL induced changes in the trabecular microarchitecture of caudal vertebrae. In summary, in adult rats a single ZOL injection inhibited OVX-induced changes in lumbar vertebral bone microarchitecture and strength.Keywords Bisphosphonate Á Bone architecture/ structure Á Osteoporosis Á Animal model Bisphosphonates inhibit bone resorption and are commonly used to treat osteoporotic patients. They slow the process of bone loss and reduce the risk of fracture by maintaining bone mass and microstructure [1][2][3]. Zoledronic acid (ZOL) is a potent bisphosphonate that has recently been shown to significantly reduce fracture risk in osteoporotic patients who received once-yearly doses [4,5]. As the number and depth of in vivo analyses in patients are limited, animal research is ongoing to further elucidate the effects of ZOL on skeletal fragility [6][7][8][9]. Previously, we showed in a longitudinal study of adult rats that a single injection of ZOL at the time of ovariectomy (OVX) inhibited OVX-induced deterioration of bone microstructure and strength in the proximal tibiae for up to 16 weeks [10]. Furthermore, a single injection of ZOL 8 weeks after OVX inhibited further deterioration of the bone microstructure and strength in rat tibiae compared to untreated OVX rats. Other studies have shown that weekly injections of ZOL inhibit changes in bone microstructure and strength in rat vertebrae after OVX [8,9]. However, it is not known to what extent a single dose of ZOL is able to inhibit and restore OVX-induced loss of bone mass, structure, and strength in rat vertebrae.

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Section: Discussionsupporting

confidence: 92%

Influence of Early and Late Zoledronic Acid Administration on Vertebral Structure and Strength in Ovariectomized Rats

2008

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“…The rats were pairfed and allowed free access to water and standard food (CE-2, CLEA Japan Inc., Tokyo, Japan), containing 1.14% calcium, 1.06% phosphorus, and 250 IU vitamin D3 per 100 g, as previously described [1,20,31]. Osteopenia was induced by bilateral ovariectomy, with or without bilateral sciatic neurectomy (OVX or OVX + NX), which was accomplished by resecting a 10 mm segment of the nerve posterior to the hip joint.…”

Section: Experirnen Tal Designmentioning

confidence: 99%

“…Bone histomorphometry and node-strut analysis were performed with a semiautomatic graphic system as previously described [1, 20,31]. Measurements were obtained in areas 390 pm from the lowest point of the growth plate-metaphyseal junctions in the caudal direction.…”

Section: Bone Hisromorphoi?~eir~ Und Node-strut Utia1ysismentioning

confidence: 99%

Effects of h-PTH on cancellous bone mass, connectivity, and bone strength in ovariectomized rats with and without sciatic-neurectomy

KASUKAWA¹

2004

Journal of Orthopaedic Research

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The purpose of this study was to determine whether h-PTH (1 -34) treatment would recover cancellous bone connectivity and bone strength in ovariectomized (OVX) or ovariectomized and sciatic-neurectomized (OVX + NX) rats. Seven-month-old female Wistar rats were treated with h-PTH or vehicle (6.0 pg/kg, six times a week, subcutaneously) for four weeks beginning 4, 8, or 12 weeks after OVX or OVX + NX. These were compared to age-matched baseline and sham-operated groups. Right tibiae were used for bone histomorphometry and node-strut analysis, and left tibiae were used for mechanical testing. The bone formation rates in the OVX and OVX + NX rats treated with h-PTH were significantly higher than those in their baseline controls. h-PTH treatment increased the node numbers and failure energies in the OVX rats, compared to their baseline controls, at all time points. However, in the OVX + NX rats, the effects of h-PTH treatment on the node number and failure energy were observed only at four weeks after surgery, but not at eight weeks or 12 weeks after surgery. These results suggest that the lowest limit, at which trabecular connectivity and bone strength are able to be restored by h-PTH, occurred between four and eight weeks in OVX + NX rats, but not in OVX rats.h-PTH cannot recover trabecular connectivity and bone strength in advanced osteopenia.

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“…Bone histomorphometry was performed with a semiautomatic graphic system as previously described [25,26,[29][30][31]. Measurements were obtained in areas 390 m from the lowest point of the growth plate-metaphyseal junctions in the caudal direction to exclude primary spongiosa, as well as 390 m from endocortical surfaces.…”

Section: Histomorphometric and Node-strut Analysesmentioning

confidence: 99%

Histomorphometric Evaluation of the Recovering Effect of Human Parathyroid Hormone (1–34) on Bone Structure and Turnover in Streptozotocin-Induced Diabetic Rats

et al. 2000

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The purpose of this study was to determine whether human parathyroid hormone (h-PTH) enhances trabecular bone mass and connectivities that were reduced by streptozotocin (STZ)-induced diabetes in rats. Seven-month-old female Wistar rats were injected with STZ or its vehicle intraperitoneally. All vehicle-injected normal controls were sacrificed 0, 4, 6, 8, 12, 14, and 16 weeks after injection, and one-third of the STZ-injected rats were sacrificed as the baseline controls 4, 6, and 8 weeks after the injection. Eight-week h-PTH (6. 0 microg/kg, 6 times a week) or its vehicle treatment by subcutaneous injection for residual diabetic rats was started 4, 6, or 8 weeks after the STZ injection. The rats' proximal right tibiae were processed for undecalcified Villanueva bone staining sections for bone histomorphometry. Furthermore, changes in trabecular connectivities were determined by node-strut analysis. The decreased cancellous bone volume (BV/TV) and turnover in diabetic rats were recovered in all PTH-treated groups. In node-strut analysis, the node-related parameters (N.Nd/TV, NdNd/TV) were significantly increased by PTH when it was administered 4 weeks after STZ injection but were not increased when administration was started after 6 weeks. The results indicated that PTH enhanced bone turnover and bone mass but not trabecular connectivity in the late stage of diabetes in rats. Early treatment of osteoporosis is important in preventing fractures caused by decreased bone strength resulting from decreased trabecular connectivity.

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Histomorphometric Evaluation of the Effects of Ovariectomy on Bone Turnover in Rat Caudal Vertebrae

Cited by 25 publications

References 18 publications

Influence of Early and Late Zoledronic Acid Administration on Vertebral Structure and Strength in Ovariectomized Rats

Influence of Early and Late Zoledronic Acid Administration on Vertebral Structure and Strength in Ovariectomized Rats

Effects of h-PTH on cancellous bone mass, connectivity, and bone strength in ovariectomized rats with and without sciatic-neurectomy

Histomorphometric Evaluation of the Recovering Effect of Human Parathyroid Hormone (1–34) on Bone Structure and Turnover in Streptozotocin-Induced Diabetic Rats

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