Bone cell activity influences bone fragility and fracture risk

Osteoporosis is one of the major bone disorders that affects both women and men, and causes bone deterioration and bone strength. Bone remodeling maintains bone mass and mineral homeostasis through the balanced action of osteoblasts and osteoclasts, which are responsible for bone formation and bone resorption, respectively. The imbalance in bone remodeling is known to be the main cause of osteoporosis. The imbalance can be the result of the action of various molecules produced by one bone cell that acts on other bone cells and influence cell activity. The understanding of the effect of these molecules on bone can help identify new targets and therapeutics to prevent and treat bone disorders. In this article, we have focused on molecules that are produced by osteoblasts, osteocytes, and osteoclasts and their mechanism of action on these cells. We have also summarized the different pharmacological osteoporosis treatments that target different molecular aspects of these bone cells to minimize osteoporosis.

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POS0163 INCIDENT FRACTURE RISK PREDICTION USING THE FRAGILITY SCORE CALCULATED BY LUMBAR SPINE RADIOFREQUENCY ECHOGRAPHIC MULTI SPECTROMETRY (REMS) SCANS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.2311 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 294.2-294

Author(s):

D. Ciardo ◽

P. Pisani ◽

F. A. Lombardi ◽

R. Franchini ◽

F. Conversano ◽

...

Keyword(s):

Lumbar Spine ◽

Fracture Risk ◽

Fragility Fracture ◽

Osteoporotic Fractures ◽

Fragility Fractures ◽

Bone Fragility ◽

P Value ◽

T Score ◽

Caucasian Women

Background:The main consequence of osteoporosis is the occurrence of fractures due to bone fragility, with important sequelae in terms of disability and mortality. It has been already demonstrated that the information about bone mass density (BMD) alone is not sufficient to predict the risk of fragility fractures, since several fractures occur in patients with normal BMD [1].The Fragility Score is a parameter that allows to estimate skeletal fragility thanks to a trans-abdominal ultrasound scan performed with Radiofrequency Echographic Multi Spectrometry (REMS) technology. It is calculated by comparing the results of the spectral analysis of the patient’s raw ultrasound signals with reference models representative of fragile and non-fragile bones [2]. It is a dimensionless parameter, which can vary from 0 to 100, in proportion to the degree of fragility, independently from BMD.Objectives:This study aims to evaluate the effectiveness of Fragility Score, measured during a bone densitometry exam performed with REMS technology at lumbar spine, in identifying patients at risk of incident osteoporotic fractures at a follow-up period of 5 years.Methods:Caucasian women with age between 30 and 90 were scanned with spinal REMS and DXA. The incidence of osteoporotic fractures was assessed during a follow-up period of 5 years. The ability of the Fragility Score to discriminate between patients with and without incident fragility fractures was subsequently evaluated and compared with the discriminatory ability of the T-score calculated with DXA and with REMS.Results:Overall, 533 women (median age: 60 years; interquartile range [IQR]: 54-66 years) completed the follow-up (median 42 months; IQR: 35-56 months), during which 73 patients had sustained an incident fracture.Both median REMS and DXA measured T-score values were significantly lower in fractured patients than for non-fractured ones, conversely, REMS Fragility Score was significantly higher (Table 1).Table 1.Analysis of T-score values calculated with REMS and DXA and Fragility Score calculated with REMS. Median values and interquartile ranges (IQR) are reported. The p-value is derived from the Mann-Whitney test.Patients without incident fragility fracturePatients with incident fragility fracturep-valueT-score DXA[median (IQR)]-1.9 (-2.7 to -1.0)-2.6 (-3.3 to -1.7)0.0001T-score REMS[median (IQR)]-2.0 (-2.8 to -1.1)-2.7 (-3.5 to -1.9)<0.0001Fragility Score[median (IQR)]29.9 (25.7 to 36.2)53.0 (34.2 to 62.5)<0.0001By evaluating the capability to discriminate patients with/without fragility fractures, the Fragility Score obtained a value of the ROC area under the curve (AUC) of 0.80, higher than the AUC of the REMS T-score (0.66) and of the T-score DXA (0.64), and the difference was statistically significant (Figure 1).Figure 1.ROC curve comparison of Fragility Score, REMS and DXA T-score values in the classification of patients with incident fragility fractures.Furthermore, the correlation between the Fragility Score and the T-score values was low, with Pearson correlation coefficient r=-0.19 between Fragility Score and DXA T-score and -0.18 between the Fragility Score and the REMS T-score.Conclusion:The Fragility Score was found to be an effective tool for the prediction of fracture risk in a population of Caucasian women, with performances superior to those of the T-score values. Therefore, this tool presents a high potential as an effective diagnostic tool for the early identification and subsequent early treatment of bone fragility.References:[1]Diez Perez A et al. Aging Clin Exp Res 2019; 31(10):1375-1389.[2]Pisani P et al. Measurement 2017; 101:243–249.Disclosure of Interests:None declared

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Type 2 Diabetes Mellitus and Vertebral Fracture Risk

Current Osteoporosis Reports ◽

10.1007/s11914-020-00646-8 ◽

2021 ◽

Author(s):

Fjorda Koromani ◽

Samuel Ghatan ◽

Mandy van Hoek ◽

M. Carola Zillikens ◽

Edwin H. G. Oei ◽

...

Keyword(s):

Diabetes Mellitus ◽

Vertebral Fracture ◽

Fracture Risk ◽

Vertebral Fractures ◽

Bone Fragility ◽

Marrow Fat ◽

Systematic Screening ◽

Published Evidence ◽

Vertebral Fracture Risk

Abstract Purpose of Review The purpose of this review is to summarize the recently published evidence concerning vertebral fracture risk in individuals with diabetes mellitus. Recent Findings Vertebral fracture risk is increased in individuals with T2DM. The presence of vertebral fractures in T2DM is associated with increased non-vertebral fracture risk and mortality. TBS could be helpful to estimate vertebral fracture risk in individuals with T2DM. An increased amount of bone marrow fat has been implicated in bone fragility in T2DM. Results from two recent studies show that both teriparatide and denosumab are effective in reducing vertebral fracture risk also in individuals with T2DM. Summary Individuals with T2DM could benefit from systematic screening in the clinic for presence of vertebral fractures.

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Morphological studies of bone and tendon

Journal of Applied Physiology ◽

10.1152/jappl.1992.73.2.s10 ◽

1992 ◽

Vol 73 (2) ◽

pp. S10-S13 ◽

Cited By ~ 20

Author(s):

S. B. Doty ◽

E. R. Morey-Holton ◽

G. N. Durnova ◽

A. S. Kaplansky

Keyword(s):

Electron Microscopy ◽

Bone Cells ◽

Weight Bearing ◽

Light And Electron Microscopy ◽

Cell Activity ◽

Bone Cell ◽

Electron Microscopic ◽

Adult Rats ◽

Morphological Studies ◽

Metatarsal Bones

The Soviet biosatellite COSMOS 2044 carried adult rats on a spaceflight that lasted 13.8 days and was intended to repeat animal studies carried out on COSMOS 1887. Skeletal tissue and tendon from animals flown on COSMOS 2044 were studied by light and electron microscopy, histochemistry, and morphometric techniques. Studies were confined to the bone cells and vasculature from the weight-bearing tibias. Results indicated that vascular changes at the periosteal and subperiosteal region of the tibia were not apparent by light microscopy or histochemistry. However, electron microscopy indicated that vascular inclusions were present in bone samples from the flight animals. A unique combination of microscopy and histochemical techniques indicated that the endosteal osteoblasts from this same mid-diaphyseal region demonstrated a slight (but not statistically significant) reduction in bone cell activity. Electron-microscopic studies of the tendons from metatarsal bones showed a collagen fibril disorganization as a result of spaceflight. Thus changes described for COSMOS 1887 were present in COSMOS 2044, but the changes ascribed to spaceflight were not as evident.

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Secondary Osteoporosis in Men and Women: Clinical Challenge of an Unresolved Issue

The Journal of Rheumatology ◽

10.3899/jrheum.110030 ◽

2011 ◽

Vol 38 (8) ◽

pp. 1671-1679 ◽

Cited By ~ 11

Author(s):

ELISABETTA ROMAGNOLI ◽

ROMANO DEL FIACCO ◽

STEFANIA RUSSO ◽

SARA PIEMONTE ◽

FRANCESCA FIDANZA ◽

...

Keyword(s):

Fracture Risk ◽

Clinical Symptoms ◽

Bone Fragility ◽

Secondary Osteoporosis ◽

Primary Osteoporosis ◽

High Fracture ◽

Men And Women ◽

Osteoporosis In Men ◽

Prevention Of Osteoporosis ◽

A Prospective Study

Objective.To evaluate the clinical and etiological factors of osteoporosis. We also tested the FRAX algorithm to compare the assessment of fracture risk in patients with primary or secondary osteoporosis.Methods.A prospective study carried out in a large sample of 123 men and 246 women. All subjects had a biochemical, densitometric, and radiological examination of thoracic and lumbar spine.Results.The prevalence of primary (men 52.9% vs women 50%; p = nonsignificant) and secondary (men 21.1% vs women 17.5%; p = nonsignificant) osteoporosis did not differ between the sexes. In contrast, the prevalence of primary osteoporosis was significantly higher than secondary causes (p < 0.0001) in both men and women. While women came to our attention for prevention of osteoporosis, men sought help because of clinical symptoms or disease-related complications, such as fractures. As evaluated by the FRAX tool, patients with osteopenia do not need treatment, in agreement with Italian guidelines. The estimated risk of major osteoporotic and hip fractures was significantly higher in women with secondary osteoporosis compared to men and also compared to women with primary osteoporosis.Conclusion.The prevalence of secondary osteoporosis in men is similar to that in women and it is less frequent than commonly reported. In patients with secondary osteoporosis, FRAX calculation may provide an estimate of a particularly high fracture risk in patients whose bone fragility is usually attributed to another disease.

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Wnt signaling and bone cell activity

Principles of Bone Biology ◽

10.1016/b978-0-12-814841-9.00008-7 ◽

2020 ◽

pp. 177-204

Author(s):

Bart O. Williams ◽

Mark L. Johnson

Keyword(s):

Wnt Signaling ◽

Cell Activity ◽

Bone Cell

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Circadian variation in biochemical markers of bone cell activity and insulin-like growth factor-I in two-year-old horses1

Journal of Animal Science ◽

10.2527/2003.81112804x ◽

2003 ◽

Vol 81 (11) ◽

pp. 2804-2810 ◽

Cited By ~ 21

Author(s):

B. F. Jackson ◽

A. Blumsohn ◽

A. E. Goodship ◽

A. M. Wilson ◽

J. S. Price

Keyword(s):

Growth Factor ◽

Biochemical Markers ◽

Circadian Variation ◽

Cell Activity ◽

Bone Cell ◽

Insulin Like Growth Factor ◽

Factor I ◽

Growth Factor I

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Decreased potassium stimulates bone resorption

AJP Renal Physiology ◽

10.1152/ajprenal.1997.272.6.f774 ◽

1997 ◽

Vol 272 (6) ◽

pp. F774-F780 ◽

Cited By ~ 5

Author(s):

D. A. Bushinsky ◽

D. R. Riordon ◽

J. S. Chan ◽

N. S. Krieger

Keyword(s):

Bone Resorption ◽

Collagen Synthesis ◽

Cell Activity ◽

Bone Cell ◽

Osteoblastic Cell ◽

Enzyme Release ◽

Osteoblastic Cell Line ◽

Glucuronidase Activity ◽

K Concentration ◽

Low K

Metabolic acidosis induces net calcium efflux (JCa+) from cultured bone, in part, through an increase in osteoclastic resorption and a decrease in osteoblastic formation. In humans provision of base as potassium (K+) citrate, but not sodium (Na+) citrate, reduces urine Ca (UCa), and oral KHCO3 decreases bone resorption and UCa in postmenopausal women. Potassium deprivation alone leads to an increase in UCa. To determine whether decreased extracellular K+ concentration ([K+]) at a constant pH, PCO2, and [HCO-3] alters JCa+ and bone cell activity, we measured JCa+, osteoblastic collagen synthesis, and osteoclastic beta-glucuronidase release from neonatal mouse calvariae cultured for 48 h in medium of varying [K+]. Calvariae were cultured in control medium (approximately 4 mM [K+]) or medium with mildly low K+ (MLK, approximately 3 mM [K+]), very low K+ (VLK, approximately 2 mM [K+]), or extremely low K+ (ELK, approximately 1 mM [K+]) (n > or = 9 in each group). Compared with control, ELK, but not MLK or VLK, resulted in a marked increase in JCa+ and an increase in beta-glucuronidase release and a decrease in collagen synthesis. JCa+ was correlated directly with medium beta-glucuronidase activity and inversely with collagen synthesis. To determine whether the reduction in medium [K+] was associated with a decrease in intracellular pH (pHi), we measured pHi in MC3T3-E1 cells, a mouse osteoblastic cell line. Incubation in 1 mM [K+] led to a significant decrease in pHi compared with 3 mM [K+]. Thus incubation in a reduced [K+] medium stimulates JCa+ and osteoclastic enzyme release and inhibits osteoblastic collagen synthesis, which may be mediated by a reduction in bone cell pH.

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