Human parathyroid hormone(1–34) increases bone formation and strength of cortical bone in aged rats

1994 ◽  
Vol 130 (2) ◽  
pp. 201-207 ◽  
Author(s):  
Charlotte Ejersted ◽  
Troels T Andreassen ◽  
Magnus HL Nilsson ◽  
Hans Oxlund
Keyword(s):  
Parathyroid Hormone ◽  
Bone Formation ◽  
Cortical Bone ◽  
Formation Rate ◽  
The Body ◽  
Male Rats ◽  
Double Labelling ◽  
Aged Rats ◽  
Human Parathyroid Hormone ◽  
Bone Formation Rate

Ejersted C, Andreassen TT, Nilsson MHL, Oxlund H. Human parathyroid hormone(1–34) increases bone formation and strength of cortical bone in aged rats. Eur J Endocrinol 1994;130:201–7. ISSN 0804–4643 The effect of parathyroid hormone (PTH(1–34)) on mid-diaphyseal femoral cortical bone was studied in 2-year-old male rats. The rats were treated with daily injections of 1 5 nmol/kg PTH(1–34) or vehicle for 56 days, and labelled with tetracycline and calcein on day 15 and day 40, respectively. The PTH(1–34) treatment did not affect the body weights or the lengths of the femora. Fluorescence microscopy showed large intracortical cavities in the old vehicle-treated rats. After PTH treatment, double labelling and new bone formation filling in these cavities were found. Furthermore, an increased bone formation rate was observed both at the periosteum and at the endosteum. This resulted in an increase in the cross-sectional area and a decrease in the medullary area. Three-point bending analysis revealed an increase in ultimate load, ultimate stiffness, energy absorption and ultimate stress after the PTH(1–34) treatment. No differences were found between the groups regarding the hydroxyproline concentration or apparent and real densities. The ash concentration was, however, slightly reduced after PTH(1–34) treatment. The PTH(1–34) treatment of old rats induced the formation of bone both from the periosteum and endosteum, with a pronounced filling in of intracortical cavities, and, furthermore, a marked increase in the biomechanical competence of the cortical bone. Charlotte Ejersted, Department of Connective Tissue Biology, Institute of Anatomy, University of Aarhus, DK-8000 Aarhus C. Denmark

Disuse in adult male rats attenuates the bone anabolic response to a therapeutic dose of parathyroid hormone

2006 ◽  
Vol 101 (3) ◽  
pp. 881-886 ◽  
Author(s):  
Russell T. Turner ◽  
Sutada Lotinun ◽  
Theresa E. Hefferan ◽  
Emily Morey-Holton
Keyword(s):  
Parathyroid Hormone ◽  
Bone Formation ◽  
Cancellous Bone ◽  
Therapeutic Dose ◽  
Weight Bearing ◽  
Formation Rate ◽  
Hindlimb Unloading ◽  
Male Rats ◽  
Mineral Apposition Rate ◽  
Bone Formation Rate

Intermittent treatment with parathyroid hormone (PTH) increases bone formation and prevents bone loss in hindlimb-unloaded (HLU) rats. However, the mechanisms of action of PTH are incompletely known. To explore possible interactions between weight bearing and PTH, we treated 6-mo-old weight-bearing and HLU rats with a human therapeutic dose (1 μg·kg−1·day−1) of human PTH(1–34) (hPTH). Cortical and cancellous bone formation was measured in tibia at the diaphysis proximal to the tibia-fibula synostosis and at the proximal metaphysis, respectively. Two weeks of hindlimb unloading resulted in a dramatic decrease in the rate of bone formation at both skeletal sites, which was prevented by PTH treatment at the cancellous site only. In contrast, PTH treatment increased cortical as well as cancellous bone formation in weight-bearing rats. Two-way ANOVA revealed that hPTH and HLU had independent and opposite effects on all histomorphometric indexes of bone formation [mineral apposition rate (MAR), double-labeled perimeter (dLPm), and bone formation rate (BFR)] at both skeletal sites. The bone anabolic effects of weight bearing and hPTH on dLPm and BFR at the cortical site were additive, as were the effects on MAR at the cancellous site. In contrast, weight bearing and hPTH resulted in synergistic increases in cortical bone MAR and cancellous bone dLPm and BFR. We conclude that weight bearing and PTH act cooperatively to increase bone formation by resulting in site-specific additive and synergistic increases in indexes of osteoblast number and activity, suggesting that weight-bearing exercise targeted to osteopenic skeletal sites may improve the efficacy of PTH therapy for osteoporosis.

scholarly journals Sweep imaging with Fourier transform as a tool with MRI for evaluating the effect of teriparatide on cortical bone formation in an ovariectomized rat model

2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Yasutaka Sotozono ◽  
Kazuya Ikoma ◽  
Masamitsu Kido ◽  
Okihiro Onishi ◽  
Masataka Minami ◽  
...  
Keyword(s):  
Fourier Transform ◽  
Bone Formation ◽  
Cortical Bone ◽  
Bone Histomorphometry ◽  
Signal To Noise Ratio ◽  
Formation Rate ◽  
Bound Water ◽  
Proton Density ◽  
Sprague Dawley ◽  
Bone Formation Rate

Abstract Background Teriparatide (TPTD) is a drug for osteoporosis that promotes bone formation and improves bone quality. However, the effects of TPTD on cortical bone are not well understood. Sweep imaging with Fourier transform (SWIFT) has been reported as a useful tool for evaluating bound water of cortical bone, but it has yet to be used to investigate the effects of TPTD on cortical bone. This study aimed to evaluate the consequences of the effect of TPTD on cortical bone formation using SWIFT. Methods Twelve-week-old female Sprague-Dawley rats (n = 36) were reared after ovariectomy to create a postmenopausal osteoporosis model. They were divided into two groups: the TPTD and non-TPTD groups. Rats were euthanized at 4, 12, and 24 weeks after initiating TPTD treatment. Tibial bones were evaluated using magnetic resonance imaging (MRI) and bone histomorphometry. In MRI, proton density-weighted imaging (PDWI) and SWIFT imaging were performed. The signal-to-noise ratio (SNR) was calculated for each method. The same area evaluated by MRI was then used to calculate the bone formation rate by bone histomorphometry. Measurements were compared using the Mann-Whitney U-test, and a P-value of < 0.05 was considered significant. Results PDWI-SNR was not significantly different between the two groups at any time point (P = 0.589, 0.394, and 0.394 at 4, 12, and 24 weeks, respectively). Contrarily, SWIFT-SNR was significantly higher in the TPTD group than in the non-TPTD group at 4 weeks after initiating treatment, but it was not significantly different at 12 and 24 weeks (P = 0.009, 0.937, and 0.818 at 4, 12, and 24 weeks, respectively). The bone formation rate assessed by histomorphometry was significantly higher in the TPTD group than in the non-TPTD group at all timepoints (P < 0.05, all weeks). In particular, at 4 weeks, the bone formation rate was markedly higher in the TPTD group than in the non-TPTD group (P = 0.028, 1.98 ± 0.33 vs. 0.09 ± 0.05 μm3/μm2/day). Conclusions SWIFT could detect increased signals of bound water, reflecting the effect of TPTD on the cortical bone. The signal detected by SWIFT reflects a marked increase in the cortical bone formation rate.

Attenuated bone aluminum deposition in nonuremic beagles with reduced bone remodeling

1990 ◽  
Vol 258 (4) ◽  
pp. E576-E581
Author(s):  
L. D. Quarles
Keyword(s):  
Parathyroid Hormone ◽  
Bone Formation ◽  
Bone Turnover ◽  
Bone Remodeling ◽  
Aluminum Chloride ◽  
Formation Rate ◽  
Bone Formation Rate ◽  
Osteoid Surface ◽  
Aluminum Accumulation ◽  
Aluminum Deposition

Excess bone aluminum accumulates in uremic subjects after parathyroidectomy. To evaluate whether decreased bone remodeling caused by parathyroidectomy augments bone aluminum deposition, we administered aluminum chloride (0.75 mg/kg iv 3 times/wk) or vehicle to thyroparathyroidectomized (TPTX) and sham-operated (Sham) nonuremic beagles for 8 wk. TPTX alone effectively lowered plasma parathyroid hormone concentrations (8.2 +/- 2.8 vs. 27 +/- 2.2 pg/ml) and consequently suppressed bone remodeling, as evidenced by the diminished resorptive surface (0.8 +/- 0.3 vs. 4.0 +/- 0.5%), osteoid surface (0.5 +/- 0.2 vs. 13.3 +/- 2.3%), and bone formation rate (1.8 +/- 0.6 vs. 15.5 +/- 2.2%/yr) compared with untreated Shams. Aluminum treatment resulted in no further suppression of bone remodeling in TPTX dogs and did not cause osteomalacia. Aluminum-treated TPTX dogs, however, accumulated much less total bone (28.1 +/- 4.5 micrograms/g) and surface aluminum (3.8 +2- 1.4%) than similarly treated Shams (61.4 +/- 5.6 micrograms/g; 12.2 +/- 2.7%, respectively) despite displaying higher plasma aluminum concentrations (1,209 +/- 330 vs. 181 +/- 18 micrograms/l). These observations illustrate that diminished bone turnover retards rather than augments bone aluminum accumulation. Thus bone aluminum deposition after parathyroidectomy in uremic subjects is not likely to be the result of passive aluminum accumulation on inactive bone surfaces. Further studies are needed to determine whether factors, such as prior bone aluminum accumulation and/or the degree of preexistent hyperosteoidosis, modulate aluminum accumulation after parathyroidectomy.

scholarly journals The effect of high parathyroid hormone levels on the development of aluminum-induced osteomalacia in the rat.

1991 ◽  
Vol 1 (7) ◽  
pp. 970-979
Author(s):  
A J Felsenfeld ◽  
L Machado ◽  
M Rodriguez
Keyword(s):  
Parathyroid Hormone ◽  
Bone Formation ◽  
Bone Disease ◽  
Formation Rate ◽  
Aluminum Concentration ◽  
Aluminum Surface ◽  
Dialysis Patients ◽  
Bone Formation Rate ◽  
Aluminum Exposure ◽  
Relative Deficiency

A relative deficiency of parathyroid hormone (PTH) is generally observed in dialysis patients with aluminum-associated osteomalacia or aplastic bone disease. It has been suggested that high PTH levels may protect against the development of aluminum-associated bone disease. Through the use of a previously established model of aluminum-induced osteomalacia in the rat, the protective effect of PTH was evaluated. Aluminum was administered intraperitoneally at doses of 0, 5, 10, and 20 mg during a 2-day period, and rats were sacrificed 5 and 12 days after aluminum administration. PTH (bovine 1-34) was administered via a subcutaneously implanted Alzet pump at 2 U/h starting 4 days before aluminum administration and continuing until sacrifice. As the aluminum dose was increased to 20 mg, the osteoblast surface and the bone formation rate decreased. PTH supplementation increased the osteoblast surface at all doses of aluminum and increased the bone formation rate at 0 and 5 mg of aluminum. However, even with PTH supplementation, osteoblast surface decreased as the aluminum dose increased. In the absence of PTH supplementation, osteoblast surface was markedly reduced when the serum aluminum concentration was greater than 400 micrograms/liter or stainable trabecular aluminum surface exceeded 15%. When the stainable trabecular aluminum surface was greater than 12%, the bone formation rate was zero even during supplemental PTH administration. A significant correlation was observed between serum aluminum and stainable trabecular aluminum surface (r = 0.80 at 5 days and r = 0.86 at 12 days; P less than 0.001). However, after PTH administration, less stainable trabecular aluminum was present for the same serum aluminum concentration. Both with and without PTH, the slope of the correlation between serum aluminum and stainable trabecular aluminum surface was steeper at 5 days after aluminum administration than at 12 days. In conclusion, for an equivalent aluminum exposure, high PTH levels protected against the development of low turnover aluminum bone disease in the rat.

scholarly journals Sweep Imaging with Fourier Transform as a Tool for Evaluating the Effect of Teriparatide on Cortical Bone Turnover in an Ovariectomized Rat Model

2021 ◽  
Author(s):  
Sotozono Yasutaka ◽  
Kazuya Ikoma ◽  
Masamitsu Kido ◽  
Okihiro Onishi ◽  
Masataka Minami ◽  
...  
Keyword(s):  
Fourier Transform ◽  
Bone Formation ◽  
Bone Turnover ◽  
Cortical Bone ◽  
Bone Histomorphometry ◽  
Signal To Noise Ratio ◽  
Formation Rate ◽  
Proton Density ◽  
Sprague Dawley ◽  
Bone Formation Rate

Abstract Background: Teriparatide (TPTD) is a drug for osteoporosis that promotes bone formation and improves bone turnover. However, the specific effects of TPTD on cortical bone are not well understood. Sweep imaging with Fourier transform (SWIFT) has been reported as a useful tool for evaluating cortical bone, but it has yet to be used to investigate the effects of TPTD on cortical bone. This study aimed to evaluate the effects of TPTD on cortical bone turnover using SWIFT in rats. Methods: Twelve-week-old female Sprague-Dawley rats (n=36) were reared for 12 weeks after ovariectomy to create a postmenopausal osteoporosis model. They were divided into two groups: the TPTD and non-TPTD groups. Rats were euthanized at 4, 12, and 24 weeks after initiating TPTD treatment. Tibial bones were extracted and evaluated using magnetic resonance imaging (MRI) and bone histomorphometry. In MRI, proton density-weighted imaging (PDWI) and SWIFT imaging were performed. The signal-to-noise ratio (SNR) was calculated for each method. The same area evaluated by MRI was then used to calculate for the bone formation rate by bone histomorphometry . Measurements were compared using the Mann-Whitney U-test, and a P-value of <0.05 was considered significant. Results: PDWI-SNR was not significantly different between the two groups at any time point (P = 0.589, 0.394, and 0.394 at 4, 12, and 24 weeks, respectively). Contrarily, SWIFT-SNR was significantly higher in the TPTD group than in the non-TPTD group at 4 weeks after initiating treatment, but it was not significantly different at 12 and 24 weeks (P = 0.009, 0.937, and 0.818 at 4, 12, and 24 weeks, respectively). The bone formation rate was significantly higher in the TPTD group than in the non-TPTD group at all timepoints (P < 0.05, all weeks). In particular, at 4 weeks, the bone formation rate was markedly higher in the TPTD group than in the non-TPTD group (1.98±0.33 vs. 0.09±0.05 μm3/μm2/day).Conclusions: The marked increase of the bone formation rate in the cortical bone by TPTD could be measured using SWIFT. SWIFT could be an effective tool for evaluating the effects of TPTD on cortical bone turnover as images.

scholarly journals Growth Hormone and Mild Exercise in Combination Markedly Enhance Cortical Bone Formation and Strength in Old Rats*

Endocrinology ◽  
1998 ◽  
Vol 139 (4) ◽  
pp. 1899-1904 ◽  
Author(s):  
H. Oxlund ◽  
N. B. Andersen ◽  
G. Ørtoft ◽  
H. Ørskov ◽  
T. T. Andreassen
Keyword(s):  
Growth Factor ◽  
Bone Formation ◽  
Cortical Bone ◽  
Formation Rate ◽  
Breaking Load ◽  
Female Rats ◽  
Sectional Area ◽  
Cross Sectional ◽  
Bone Formation Rate ◽  
Factor I

Abstract The effects of a combination of mild exercise and GH injections on bone were studied in old female rats. Biosynthetic human GH, 2.7 mg/kg/day, was injected sc for 73 days. Exercised rats ran 8 m/min on a treadmill for 1 h/day. All rats (age 21 months old) were labeled with a tetracycline injection 56 days and a calcein injection 11 days before killing. The GH injections resulted in an 11-fold increase in femoral middiaphyseal bone formation rate and a 12% increase in cross-sectional area compared with the saline-injected group. The mild exercise doubled the mineralizing surface but did not influence the bone formation rate significantly. The combination of GH injections plus exercise, however, resulted in a further increase of 39% in bone formation rate, primarily at the anterolateral aspects, and an increase of 5% in cross-sectional area compared with the group injected with GH only. The femur ultimate breaking load was increased by 37% and the stiffness by 42% in the group injected with GH compared with the saline-injected group. Exercise alone did not influence the femur mechanical properties. The combination of GH injections plus exercise induced a 4% further increase in ultimate breaking load and 7% further increase in stiffness compared with the group injected with GH alone. The GH injections induced a 117% increase in serum insulin-like growth factor I. The GH-insulin-like growth factor I axis stimulates recruitment of osteoblast precursor cells, resulting in increased bone formation at the periosteal surface. GH injections and mild excercise in combination modulate and increase further the formation and strength of cortical bone in old female rats.

scholarly journals The Effects of Parathyroid Hormone Applied at Different Regimes on the Trochanteric Region of the Femur in Ovariectomized Rat Model of Osteoporosis

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
M. Tezval ◽  
A. Banhardt ◽  
S. Sehmisch ◽  
L. Kolios ◽  
U. Schmelz ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Bone Formation ◽  
Cross Sections ◽  
Rat Model ◽  
Sham Group ◽  
Formation Rate ◽  
Sprague Dawley ◽  
Bone Formation Rate ◽  
Sprague Dawley Rats ◽  
Trochanteric Region

This study aims to investigate the effects of two application frequencies of parathyroid hormone on the trochanteric region of rat femur. Forty-three-month-old female Sprague-Dawley rats were divided into 4 groups (n=10/group). Three groups were ovariectomized, and 8 weeks later they were administered the following treatments (5 weeks): soy-free diet (OVX), subcutaneously injected PTH (0.040 mg/kg) 5 days a week (PTH 5x/w), subcutaneously injected PTH (0.040 mg/kg) every 2 days (PTH e2d), and a sham group. The values of the biomechanical and histomorphometric parameters showed higher results in 5x/w animals in comparison to the OVX and PTH 2ed groups. The ratio between bone diameter/marrow diameter (B.Dm/Ma.Dm) in subtrochanteric cross sections did not show any significant differences between PTH 5x/w and PTH e2d. The increased bone formation rate was observed under PTH treatment in both groups mainly at the endosteal side. The endosteum seems here to be one of the targets of PTH with an accelerate bone formation and a pronounced filling-in of intracortical cavities with higher intensity for the PTH 5x/w in comparison to PTH e2d rats.

Tetracycline Double Labelling Tracing Investigation for In Vivo Osteogenetic Course of PDLLA/HA Composite

2011 ◽  
Vol 685 ◽  
pp. 394-398
Author(s):  
Xin Yu Wang ◽  
Xue Zhi Shan ◽  
Yin Chao Han ◽  
Shi Pu Li
Keyword(s):  
Bone Formation ◽  
Early Stage ◽  
Dynamic Balance ◽  
Formation Rate ◽  
Double Labelling ◽  
Image Analysis System ◽  
Bone Formation Rate ◽  
Calculation Results ◽  
Analysis System

The PDLLA(DL-Poly lactic acids)/HA(Hydroxyapatite) composite and pure PDLLA control were implanted in bone for test. Using fluorescent pictures of tetracycline double label and advanced image analysis system, the trend of bone-formation rate for the implanting region of PDLLA/HA composite was obtained via morphometry measurement of the slices labeled with tetracycline. The investigation and calculation results show that, the formation rate of new bone is stable and high (reaches 2.044μm/day) in the early stage of implantation for the PDLLA/HA composite, demonstrating the advantageous capability of bone formation for the composite. The formation rate of new bone seems to decrease continuously with time, and then the bone formation and bone decomposition tend towards equilibration. Namely, the dynamic balance of bony tissue’s metabolism is maintained.

Dietary Calcium Supplementation Suppresses Bone Formation in Magnesium-Deficient Rats

2006 ◽  
Vol 76 (3) ◽  
pp. 111-116 ◽  
Author(s):  
Hiroshi Matsuzaki ◽  
Misao Miwa
Keyword(s):  
Bone Formation ◽  
Calcium Supplementation ◽  
Control Diet ◽  
Formation Rate ◽  
Dietary Calcium ◽  
Mineral Apposition Rate ◽  
Control Group ◽  
Deficient Diet ◽  
Bone Formation Rate ◽  
Male Wistar Rats

The purpose of this study was to clarify the effects of dietary calcium (Ca) supplementation on bone metabolism of magnesium (Mg)-deficient rats. Male Wistar rats were randomized by weight into three groups, and fed a control diet (control group), a Mg-deficient diet (Mg- group) or a Mg-deficient diet having twice the control Ca concentrations (Mg-2Ca group) for 14 days. Trabecular bone volume was significantly lower in the Mg - and Mg-2Ca groups than in the control group. Trabecular number was also significantly lower in the Mg - and Mg-2Ca groups than in the control group. Mineralizing bone surface, mineral apposition rate (MAR), and surface referent bone formation rate (BFR/BS) were significantly lower in the Mg - and Mg-2Ca groups than in the control group. Furthermore, MAR and BFR/BS were significantly lower in the Mg-2Ca group than in the Mg - group. These results suggest that dietary Ca supplementation suppresses bone formation in Mg-deficient rats.

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