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.

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.

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 Plasma total versus bone alkaline phosphatase as markers of bone turnover in hemodialysis patients.

1996 ◽  
Vol 7 (3) ◽  
pp. 506-512
Author(s):  
P Ureña ◽  
M Hruby ◽  
A Ferreira ◽  
K S Ang ◽  
M C de Vernejoul
Keyword(s):  
Alkaline Phosphatase ◽  
Bone Formation ◽  
Bone Turnover ◽  
Bone Disease ◽  
Formation Rate ◽  
Bone Alkaline Phosphatase ◽  
Hemodialysis Patients ◽  
High Turnover ◽  
Bone Formation Rate ◽  
Markers Of Bone Turnover

Plasma total versus bone alkaline phosphatase as markers of bone turnover in hemodialysis patients. Plasma bone-specific alkaline phosphatase (bAP) has been demonstrated to be more reliable than total alkaline phosphatases (tAP) in providing information about bone turnover in patients with metabolic bone diseases. This study surveyed 42 hemodialysis patients who underwent a systematic transiliac bone biopsy for histomorphometry study. Plasma bAP was determined by using a new immunoassay (Tandem-R Ostase, Hybritech, Liège, Belgium). Plasma bAP values were compared with those of two other plasma markers of bone metabolism, namely tAP and intact parathyroid hormone (iPTH), for the correlations with bone histomorphometric parameters. Patients with high-turnover bone disease (HTBD) (N = 32) had significantly higher plasma bAP levels than patients with normal or low bone turnover (N/LTBD) (N = 10) (66.9 +/- 63.5 ng/mL versus 10.8 +/- 4.2 ng/mL, respectively). Bone formation and resorption were highly correlated in these patients, and plasma bAP levels were positively correlated with bone resorption parameters, including osteoclast surface (r = 0.39, P < 0.0001) and osteoclast number/mm2 (r = 0.36, P < 0.001), and with bone formation parameters, osteoblast surface (r = 0.50, P < 0.005), and bone formation rate (r = 0.91, P < 0.0001). The bone formation rate was better correlated with plasma bAP levels than with either plasma tAP or iPTH concentrations. Plasma bAP level equal or higher than 20 ng/mL, either alone or combined with plasma iPTH of 200 pg/mL, had the highest sensitivity, specificity, and predictability values for the diagnosis of high-turnover bone disease, and formally excluded patients with normal or LTBD. In conclusion, plasma bAP can be measured with a reliable immunoassay in hemodialysis patients. It represents a highly sensitive and specific biochemical marker of skeletal remodeling in these patients. Therefore, both serum iPTH and bAP are complementary in diagnoses of the type of renal osteodystrophy.

The rate of cancellous bone formation falls immediately after ovariectomy in the rat

1994 ◽  
Vol 142 (1) ◽  
pp. 119-125 ◽  
Author(s):  
J M Lean ◽  
J W M Chow ◽  
T J Chambers
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Formation Rate ◽  
Mineral Apposition Rate ◽  
Relative Reduction ◽  
Bone Formation Rate ◽  
Similar Action ◽  
Oestrogen Deficiency ◽  
Before And After ◽  
Relative Deficiency

Abstract We have recently found that administration of oestradiol-17β (OE2) to rats stimulates trabecular bone formation. It is not known, however, whether oestrogen has a similar action on bone formation rate under physiological circumstances. Oestrogen is known to suppress bone resorption, and oestrogen-deficient states in the rat, as in humans, are associated with an increase in bone resorption that entrains an increase in bone formation. To see if the latter masks a relative reduction in bone formation, due to oestrogen deficiency, we measured bone formation very early after ovariectomy, before the resorption-induced increase in bone formation becomes established. To do this, rats were administered fluorochrome labels before and after ovariectomy, spaced at weekly intervals in the first, and 3-day intervals in the second experiment. In both experiments there was a decrease in indices of bone formation in the labelling interval immediately following ovariectomy such that, using the shorter fluorochrome intervals, the mineral apposition rate fell to 69%, the double-labelled surface to 45%, and the bone formation rate to 36% of sham-ovariectomized levels. The reduction was not sustained in the subsequent label intervals, presumably masked by the increase in bone formation attributable to increased resorption. These results suggest that if bone formation is assessed before this resorption-entrained increase in bone formation occurs, oestrogen deficiency is associated with a reduction in dynamic indices of bone formation. Thus, these experiments suggest that oestrogen stimulates bone formation under physiological circumstances, and that the osteopaenia that follows oestrogen deficiency may be attributable not only to an increase in bone resorption, but also to a relative deficiency in bone formation. Journal of Endocrinology (1994) 142, 119–125

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

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.

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.

Regulation of bone repletion in rats subjected to varying low-calcium stress

1984 ◽  
Vol 246 (2) ◽  
pp. R190-R196 ◽  
Author(s):  
R. H. Drivdahl ◽  
C. C. Liu ◽  
D. J. Baylink
Keyword(s):  
Bone Formation ◽  
Formation Rate ◽  
Bone Volume ◽  
Strong Positive Correlation ◽  
Sprague Dawley ◽  
Bone Formation Rate ◽  
Osteoblast Activity ◽  
Calcium Stress ◽  
Sprague Dawley Rats ◽  
Very High

Weanling Sprague-Dawley rats subjected to varying degrees of low-Ca dietary stress (depletion) showed graded increases in the rate of endosteal bone formation when normal dietary Ca was restored (repletion). There was a strong positive correlation between the rate of bone resorption in depletion and the rate of bone formation attained after 1 wk of repletion. However, bone formation declined rapidly within the first 4 wk of repletion, despite the persistence of a substantial endosteal bone volume deficit. Furthermore the medullary area (indicative of bone volume) did not by itself determine the bone formation rate. Bone volume in test groups was restored to control levels after 6 mo of repletion, and this result could be predicted by a kinetic analysis. Thus, although very high rates of formation in early repletion decline rapidly, smaller increments relative to controls must be sustained for long periods. Our data indicate that increased formation rats at all stages of repletion are a consequence of elevations in both osteoblast number and osteoblast activity.

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