Continuous fluoride treatment increase wall thickness and bone volume in spinal crush fracture osteoporosis —pulse treatment preserve bone mass

We previously showed that conditional disruption of the Phd2 gene in chondrocytes led to a massive increase in long bone trabecular bone mass. Loss of Phd2 gene expression or inhibition of PHD2 activity by a specific inhibitor resulted in a several-fold compensatory increase in Phd3 expression in chondrocytes. To determine if expression of PHD3 plays a role in endochondral bone formation, we conditionally disrupted the Phd3 gene in chondrocytes by crossing Phd3 floxed (Phd3flox/flox) mice with Col2α1-Cre mice. Loss of Phd3 expression in the chondrocytes of Cre+; Phd3flox/flox conditional knockout (cKO) mice was confirmed by real time PCR. At 16 weeks of age, neither body weight nor body length was significantly different in the Phd3 cKO mice compared to Cre−; Phd3flox/flox wild-type (WT) mice. Areal BMD measurements of total body as well as femur, tibia, and lumbar skeletal sites were not significantly different between the cKO and WT mice at 16 weeks of age. Micro-CT measurements revealed significant gender differences in the trabecular bone volume adjusted for tissue volume at the secondary spongiosa of the femur and the tibia for both genotypes, but no genotype difference was found for any of the trabecular bone measurements of either the femur or the tibia. Trabecular bone volume of distal femur epiphysis was not different between cKO and WT mice. Histology analyses revealed Phd3 cKO mice exhibited a comparable chondrocyte differentiation and proliferation, as evidenced by no changes in cartilage thickness and area in the cKO mice as compared to WT littermates. Consistent with the in vivo data, lentiviral shRNA-mediated knockdown of Phd3 expression in chondrocytes did not affect the expression of markers of chondrocyte differentiation (Col2, Col10, Acan, Sox9). Our study found that Phd2 but not Phd3 expressed in chondrocytes regulates endochondral bone formation, and the compensatory increase in Phd3 expression in the chondrocytes of Phd2 cKO mice is not the cause for increased trabecular bone mass in Phd2 cKO mice.

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Evaluation of zygomatic bone region for placement of quad zygomatic implants using CBCT in postmenopausal women

IP International Journal of Maxillofacial Imaging ◽

10.18231/j.ijmi.2021.010 ◽

2021 ◽

Vol 7 (2) ◽

pp. 48-53

Author(s):

Neelam Manoj Vaibhav ◽

Ramesh Amirisetty ◽

Rajesh Nichenametla ◽

Gonabhavi Siri Chandana ◽

Santhi Prathyusha M ◽

...

Keyword(s):

Bone Resorption ◽

Bone Mass ◽

Postmenopausal Women ◽

Bone Volume ◽

Primary Osteoporosis ◽

Alveolar Ridge ◽

Age Group ◽

Zygomatic Bone ◽

Zygomatic Implants ◽

Bone To Implant Contact

Insufficient height and width of the alveolar ridge at the implant site remains with inadequate bone volume following extraction in older age people especially in postmenopausal women. Postmenopausal women are susceptible to primary osteoporosis where more bone resorption than formation is seen resulting in decreased bone mass. Hence the present study aims to evaluate the zygomatic bone region for placement of quad zygomatic implants using CBCT.: A total of 120 CBCT images of female patients who were between the age group of 45 yrs to 65 yrs were taken. The zygomatic bone was evaluated for pneumatisation zones and thickness of zygomatic bone at three different regions i.e., superior, middle and inferior at nine points on zygoma bone along with bone to implant contact (BIC) region using virtual software. The largest thickness in the superior, middle and inferior regions were at Point A2(8.01+/-2.10 mm), Point B2 (7.01+/-1.62 mm), and Point C1 (6.65+/-1.64 mm), respectively. The virtually placed implants at Point A3 (15.92+/-4.16 mm) and Point B2 (12.02+/-3.62 mm) had the highest BICs. : To obtain the largest BICs, results suggested that the posterosuperior region (Point A3) and the centre of zygoma (Point B1) were the optimal places for the placement of quad zygomatic implants.

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Mice Lacking β-Adrenergic Receptors Have Increased Bone Mass but Are Not Protected from Deleterious Skeletal Effects of Ovariectomy

Endocrinology ◽

10.1210/en.2008-0843 ◽

2008 ◽

Vol 150 (1) ◽

pp. 144-152 ◽

Cited By ~ 52

Author(s):

M. L. Bouxsein ◽

M. J. Devlin ◽

V. Glatt ◽

H. Dhillon ◽

D. D. Pierroz ◽

...

Keyword(s):

Bone Mineral Density ◽

Body Weight ◽

Bone Mass ◽

Trabecular Bone ◽

Adrenergic Receptors ◽

Bone Volume ◽

Trabecular Bone Volume ◽

Mineral Density ◽

Adrenergic Signaling ◽

Β Adrenergic Receptors

Activation of β2-adrenergic receptors inhibits osteoblastic bone formation and enhances osteoclastic bone resorption. Whether β-blockers inhibit ovariectomy-induced bone loss and decrease fracture risk remains controversial. To further explore the role of β-adrenergic signaling in skeletal acquisition and response to estrogen deficiency, we evaluated mice lacking the three known β-adrenergic receptors (β-less). Body weight, percent fat, and bone mineral density were significantly higher in male β-less than wild-type (WT) mice, more so with increasing age. Consistent with their greater fat mass, serum leptin was significantly higher in β-less than WT mice. Mid-femoral cross-sectional area and cortical thickness were significantly higher in adult β-less than WT mice, as were femoral biomechanical properties (+28 to +49%, P < 0.01). Young male β-less had higher vertebral (1.3-fold) and distal femoral (3.5-fold) trabecular bone volume than WT (P < 0.001 for both) and lower osteoclast surface. With aging, these differences lessened, with histological evidence of increased osteoclast surface and decreased bone formation rate at the distal femur in β-less vs. WT mice. Serum tartrate-resistance alkaline phosphatase-5B was elevated in β-less compared with WT mice from 8–16 wk of age (P < 0.01). Ovariectomy inhibited bone mass gain and decreased trabecular bone volume/total volume similarly in β-less and WT mice. Altogether, these data indicate that absence of β-adrenergic signaling results in obesity and increased cortical bone mass in males but does not prevent deleterious effects of estrogen deficiency on trabecular bone microarchitecture. Our findings also suggest direct positive effects of weight and/or leptin on bone turnover and cortical bone structure, independent of adrenergic signaling. Mice lacking ß-adrenergic receptors have increased body weight, bone mineral density, and bone turnover versus controls, but are not protected from bone loss due to deficiency of estrogens..

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Loss of Gsα in the Postnatal Skeleton Leads to Low Bone Mass and a Blunted Response to Anabolic Parathyroid Hormone Therapy

Journal of Biological Chemistry ◽

10.1074/jbc.m115.679753 ◽

2015 ◽

Vol 291 (4) ◽

pp. 1631-1642 ◽

Cited By ~ 23

Author(s):

Partha Sinha ◽

Piia Aarnisalo ◽

Rhiannon Chubb ◽

Ingrid J. Poulton ◽

Jun Guo ◽

...

Keyword(s):

Parathyroid Hormone ◽

Bone Formation ◽

Bone Mass ◽

Trabecular Bone ◽

Phospholipase C ◽

Osteoblast Differentiation ◽

Bone Volume ◽

Trabecular Bone Volume ◽

Male And Female ◽

Osteoblast Lineage

Parathyroid hormone (PTH) is an important regulator of osteoblast function and is the only anabolic therapy currently approved for treatment of osteoporosis. The PTH receptor (PTH1R) is a G protein-coupled receptor that signals via multiple G proteins including Gsα. Mice expressing a constitutively active mutant PTH1R exhibited a dramatic increase in trabecular bone that was dependent upon expression of Gsα in the osteoblast lineage. Postnatal removal of Gsα in the osteoblast lineage (P-GsαOsxKO mice) yielded markedly reduced trabecular and cortical bone mass. Treatment with anabolic PTH(1–34) (80 μg/kg/day) for 4 weeks failed to increase trabecular bone volume or cortical thickness in male and female P-GsαOsxKO mice. Surprisingly, in both male and female mice, PTH administration significantly increased osteoblast numbers and bone formation rate in both control and P-GsαOsxKO mice. In mice that express a mutated PTH1R that activates adenylyl cyclase and protein kinase A (PKA) via Gsα but not phospholipase C via Gq/11 (D/D mice), PTH significantly enhanced bone formation, indicating that phospholipase C activation is not required for increased bone turnover in response to PTH. Therefore, although the anabolic effect of intermittent PTH treatment on trabecular bone volume is blunted by deletion of Gsα in osteoblasts, PTH can stimulate osteoblast differentiation and bone formation. Together these findings suggest that alternative signaling pathways beyond Gsα and Gq/11 act downstream of PTH on osteoblast differentiation.

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Fluoride Treatment Increased Serum IGF-1, Bone Turnover, and Bone Mass, but Not Bone Strength, in Rabbits

Calcified Tissue International ◽

10.1007/s002239900299 ◽

1997 ◽

Vol 61 (1) ◽

pp. 77-83 ◽

Cited By ~ 55

Author(s):

C. H. Turner ◽

L. P. Garetto ◽

A. J. Dunipace ◽

W. Zhang ◽

M. E. Wilson ◽

...

Keyword(s):

Bone Mass ◽

Bone Turnover ◽

Bone Strength ◽

Fluoride Treatment

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Trabecular bone remodeling after seven days of weightlessness exposure (BIOCOSMOS 1667)

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1988.255.2.r243 ◽

1988 ◽

Vol 255 (2) ◽

pp. R243-R247 ◽

Cited By ~ 12

Author(s):

L. Vico ◽

D. Chappard ◽

S. Palle ◽

A. V. Bakulin ◽

V. E. Novikov ◽

...

Keyword(s):

Bone Mass ◽

Trabecular Bone ◽

Lumbar Vertebrae ◽

Bone Volume ◽

Male Rats ◽

Long Bones ◽

Trabecular Bone Volume ◽

Detectable Change ◽

Femoral Metaphysis ◽

Trabecular Bone Mass

Seven male rats were exposed to 7 days of weightlessness in the Soviet mission COSMOS 1667 and compared with seven control rats by bone histomorphometric methods. In proximal tibial metaphysis, the trabecular bone volume was markedly reduced in flight animals. Trabeculae were decreased in number and thickness; this probably leads to alteration of bone mechanical properties. Formation activity (reflected by measurements of osteoid seams) was decreased at trabecular and endosteal levels. Resorption activity (estimated by count of osteoclast number and active resorption surfaces using a histoenzymologic method) remained unchanged. The imbalance between these cellular activities appears to be responsible for the loss of trabecular bone mass. In proximal femoral metaphysis, measurements were performed in an area located under the muscular insertions. The trabecular bone volume, despite a slight decrease in flight rats, was not significantly different from that of control rats. Furthermore, osteoclastic and osteoid parameters were unchanged. Differential responses between these two long bones need additional investigations. In thoracic and lumbar vertebrae no detectable change in bone mass and bone resorption parameters was found.

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PPAR gamma-null mice have increased cancellous bone volume but low bone mass

Bone ◽

10.1016/j.bone.2011.03.445 ◽

2011 ◽

Vol 48 ◽

pp. S189-S190

Author(s):

D.D. Pierroz ◽

H. Fu ◽

B. Desvergne ◽

S.L. Ferrari

Keyword(s):

Bone Mass ◽

Cancellous Bone ◽

Ppar Gamma ◽

Bone Volume ◽

Low Bone Mass

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Anabolic Effect of Estrogen Replacement on Bone in Postmenopausal Women with Osteoporosis: Histomorphometric Evidence in a Longitudinal Study1

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.86.1.7161 ◽

2001 ◽

Vol 86 (1) ◽

pp. 289-295

Author(s):

Gautam Khastgir ◽

John Studd ◽

Nigel Holland ◽

Jamshid Alaghband-Zadeh ◽

Simon Fox ◽

...

Keyword(s):

Bone Mineral Density ◽

Postmenopausal Women ◽

Bone Mineral ◽

Cancellous Bone ◽

Wall Thickness ◽

Bone Volume ◽

Anabolic Effect ◽

Mineral Density ◽

Bone Biopsies ◽

Bone Gain

It is well recognized that estrogen (E2) prevents postmenopausal bone loss by suppressing bone resorption. Despite evidence that E2 may also stimulate bone formation in animals, an anabolic effect in humans is still controversial. To investigate this, we studied 22 older postmenopausal females, with a mean age of 65.4 yr and mean interval of 16.9 yr since menopause and low bone mineral density. Transcortical iliac bone biopsies were performed before and 6 yr after E2 replacement therapy (ERT) [75 mg percutaneous E2 replaced 6-monthly plus oral medroxy progesterone acetate (5 mg daily) for 10 days each calendar month]. The mean serum E2 level after 6 yr of treatment was 1077 (range, 180-2568) pmol/L. Bone mineral density improved in every patient, with a median increase of 31.4% at the lumbar spine and 15.1% at the proximal femur. Bone histomorphometry showed an increase in cancellous bone volume from 10.75% to 17.31% (P < 0.001). The wall thickness after 6 yr of E2 treatment was 38.30 μm compared with 31.20 μm before commencement of ERT (P < 0.0005), indicating net bone gain. This is the first report showing histological evidence for an increase in cancellous bone volume, together with an increase in wall thickness, in a longitudinal follow-up study of ERT in older postmenopausal women. Our results show that E2 is capable of exerting an anabolic effect in women with osteoporosis, even when started well into the menopause.

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Low-dose PTH increases osteoblast activity via decreased Mef2c/Sost in senescent osteopenic mice

Journal of Endocrinology ◽

10.1530/joe-14-0249 ◽

2014 ◽

Vol 223 (1) ◽

pp. 25-33 ◽

Cited By ~ 14

Author(s):

Zuzana Saidak ◽

Carole Le Henaff ◽

Sofia Azzi ◽

Caroline Marty ◽

Pierre J Marie

Keyword(s):

Bone Formation ◽

Bone Mass ◽

Low Dose ◽

Standard Dose ◽

Bone Microarchitecture ◽

Bone Volume ◽

Mineral Apposition Rate ◽

Micro Computed Tomography ◽

Trabecular Thickness ◽

Osteoblast Activity

Intermittent administration of parathyroid hormone (PTH) 1–34 at a standard dose has been shown to induce anabolic effects in bone. However, whether low-dose PTH promotes bone formation during senescence is unknown. To address this issue, we determined the effects of low-dose PTH and analysed the underlying mechanisms in prematurely senescent mice that display osteopenia. Treatment of 9-week-old Samp6 mice for 6 weeks with PTH at a standard dose (100 μg/kg per day) increased vertebral and femoral bone mass and improved bone microarchitecture as a result of increased bone-forming surfaces and mineral apposition rate (MAR). At a tenfold lower dose (10 μg/kg per day), PTH increased axial bone volume and trabecular thickness, as detected by bone histomorphometry but not by micro-computed tomography analysis. This anabolic effect resulted from increased osteoblast activity, as reflected by increased serum N-terminal propeptide of type 1 procollagen (P1NP) levels and MAR, with unchanged bone-forming surface or osteoblast surface. Mechanistically, low-dose PTH increased the expression of osteoblast markers in bone marrow stromal cells and mature osteoblasts, which was associated with increased expression of the Wnt effector Wisp1. Moreover, low-dose PTH decreased the expression of the Mef2c transcription factor, resulting in decreased Sost expression in osteoblasts/osteocytes. These results indicate that PTH at a low dose is effective at promoting bone formation and increased bone volume in senescent osteopenic mice through increased osteoblast activity and modulation of specific Wnt effectors, which raises the potential therapeutic use of intermittent PTH at low dose to increase bone forming activity and bone mass in skeletal senescence.

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