Bisphosphonates in the treatment of metabolic bone diseases

Osteoporosis is a disease characterized by low bone mass associated with the deterioration of microarchitecture, due to an imbalance either in high bone resorption or low bone formation or in both, leading to a high risk of fractures. Bisphosphonates are medications which reduce the ability of osteoclasts to induce bone resorption and consequently improve the balance between resorption and formation. There are bisphosphonates approved for the prevention and treatment of osteoporosis. Administration can be oral (daily, weekly or monthly) or intravenous (quarterly or yearly). These medications are well tolerated and with the correct instructions of administration have a good safety profile. Serious side effects, such as, osteonecrosis of jaw is very rare. Bisphosphonates are the most prescribed medication for the treatment of osteoporosis.

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Bone diseases, skeletal dysplasias, disorders of collagen

10.1093/med/9780199592630.003.0005 ◽

2012 ◽

Keyword(s):

Connective Tissue ◽

Bone Fragility ◽

Bone Diseases ◽

Dentinogenesis Imperfecta ◽

Low Bone Mass ◽

Bone Deformity ◽

Metabolic Bone Diseases ◽

Skeletal Dysplasias ◽

Metabolic Bone ◽

Collagen Genes

Metabolic bone diseases 330Skeletal dysplasias 333The osteochondroses 343Heritable disorders of connective tissue 346• Principal features are bone fragility and low bone mass leading to fractures and bone deformity with growth retardation.• Ligamentous laxity, dentinogenesis imperfecta, and blue scleral hue are variable features. 90% of OI dominantly inherited due to defects in the type ↑ collagen genes ...

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Automated HPLC Assay for Urinary Collagen Cross-links: Effect of Age, Menopause, and Metabolic Bone Diseases

Clinical Chemistry ◽

10.1373/clinchem.2008.105262 ◽

2008 ◽

Vol 54 (9) ◽

pp. 1546-1553 ◽

Cited By ~ 24

Author(s):

Marius E Kraenzlin ◽

Claude A Kraenzlin ◽

Christian Meier ◽

Cecilia Giunta ◽

Beat Steinmann

Keyword(s):

Bone Resorption ◽

Premenopausal Women ◽

Reference Intervals ◽

Bone Diseases ◽

Hplc Assay ◽

Cross Link ◽

Metabolic Bone Diseases ◽

Metabolic Bone ◽

Automated Hplc ◽

Cross Links

Abstract Background: The pyridinium cross-links pyridinoline (PYD) and deoxypyridinoline (DPD) are established markers of bone resorption. We evaluated the analytical and clinical performance of a commercially available PYD HPLC assay and established reference intervals in children and adults. Methods: We used a commercially available reagent set (Chromsystems Instruments & Chemicals) to measure PYD and DPD in 319 healthy controls (156 premenopausal women, 80 healthy men, and 83 healthy children age 1 month to 14 years) and 397 patients with metabolic bone diseases (postmenopausal osteoporosis, n = 175; male osteoporosis, n = 176; hyperparathyroidism, n = 17; hyperthyroidism, n = 19; Paget disease, n = 10). Results: The mean intraassay and interassay CVs were <6% and <8% for both PYD and DPD, respectively. The reference interval was constant for premenopausal women in the age group 20–49 years. In men, cross-link values peaked at 20–29 years and decreased thereafter. Women with postmenopausal osteoporosis had significantly higher PYD (51%) and DPD (58%) values compared to premenopausal women. Similar results were found in osteoporotic men. In children the highest values were found in the first weeks and months after birth, followed by a decrease of 50%–60% at age 11–14 years. In metabolic bone diseases cross-link concentrations were significantly increased. The DPD:PYD ratio (mean value approximately 0.2) was remarkably constant in all populations evaluated. Conclusions: The automated HPLC assay is a precise and convenient method for PYD and DPD measurement. We established reference intervals for adult women and men and for children up to 14 years old. The cross-link concentrations we determined by use of this HPLC method confirm its clinical value in enabling identification of increased bone resorption in patients with metabolic bone diseases.

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Alpinetin Inhibits RANKL-Induced Osteoclastogenesis and Ovariectomy-Induced Bone Loss by Modulating NFATc1 Transcription and Lysosomal Function

10.21203/rs.3.rs-132706/v1 ◽

2020 ◽

Author(s):

Rongxin He ◽

Jinwei Lu ◽

Yazhou Chen ◽

Yong Li ◽

Chenyi Ye ◽

...

Keyword(s):

Bone Resorption ◽

Bone Loss ◽

Bone Matrix ◽

Osteoclast Differentiation ◽

Estrogen Deficiency ◽

Bone Diseases ◽

Dependent Manner ◽

Metabolic Bone Diseases ◽

Lysosomal Function ◽

Metabolic Bone

Abstract BackgroundPostmenopausal osteoporosis is a chronic metabolic bone disease caused by excessive osteoclast activation, and osteoclasts are considered to be the sole participants in the degeneration and resorption of bone matrix for controlling bone integrity and continuity. The biological functions of osteoclasts depend critically on the number and activity of fused polykaryon. Hence, targeting osteoclast differentiation and activity can modulate bone resorption and alleviate osteoporosis. Alpinetin is widely used for excellent anti-inflammatory activities and little side-effect, but its role in osteoporosis remains unknown.ResultsIn this study, we investigated for the first time the ability of alpinetin to inhibit estrogen deficiency-induced bone loss. Alpinetin significantly reduced the expression levels of NFATc1 and its downstream genes, thereby inhibiting osteoclast differentiation in a concentration- and time-dependent manner. Additionally, alpinetin inhibited F-actin ring formation and bone resorption, as well as reduced the activation levels of NF-κB, ERK, and AKT signaling cascades. In mature osteoclasts, alpinetin remarkably inhibited integrin-mediated migration and lysosomal biogenesis and trafficking by modulating the PKCβ/TFEB and ATG5/LC3 axes. Importantly, alpinetin treatment in mice alleviated ovariectomy-induced bone volume loss. ConclusionOur findings strongly suggest that alpinetin plays a significant role in the regulation of NFATc1 production for the differentiation of osteoclasts and inhibits integrin-mediated cell migration and lysosomal function in mature osteoclasts, thus weaken the increased osteolytic ability due to estrogen deficiency. Alpinetin may represent a promising agent for the treatment of osteoporosis and other metabolic bone diseases.

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Hypercalciuria is a common and important finding in postmenopausal women with osteoporosis

Acta Endocrinologica ◽

10.1530/eje.0.1490209 ◽

2003 ◽

Vol 149 (3) ◽

pp. 209-213 ◽

Cited By ~ 47

Author(s):

S Giannini ◽

M Nobile ◽

L Dalle Carbonare ◽

MG Lodetti ◽

S Sella ◽

...

Keyword(s):

Bone Density ◽

Bone Loss ◽

Bone Mass ◽

Urinary Calcium ◽

Bone Diseases ◽

Calcium Excretion ◽

Primary Osteoporosis ◽

Low Bone Mass ◽

Metabolic Bone Diseases ◽

Metabolic Bone

OBJECTIVE AND DESIGN: The prevalence and the effects of hypercalciuria on bone in patients with primary osteoporosis are poorly defined. We therefore retrospectively analyzed the data of 241 otherwise healthy women. They were 45-88 years of age and had been referred for their first visit to our Unit for Metabolic Bone Diseases over a 2-year period because of primary osteoporosis (bone density T-score < -2.5). METHODS: The main parameters of calcium and skeletal metabolism had been analyzed in all subjects. This population was then divided into two groups, according to the presence (HC+) or absence (HC-) of hypercalciuria. RESULTS: Elevated urinary calcium was present in 19% of the subjects. Due to the selection criteria, spinal and femoral bone loss was similar in the two groups. Urinary calcium, phosphate and fractional calcium excretion were higher in hypercalciuric patients. In a logistic regression model, the higher the Tm of phosphate, the lower the risk of hypercalciuria (odds ratio 0.33, confidence interval 0.18-0.62). On the contrary, hypercalciuria was the most important predictor of low bone mass in HC+ (accounting for more than 50% of the variance in spinal bone density). CONCLUSIONS: Hypercalciuria is a common feature in postmenopausal bone loss. Since increased urinary calcium excretion and low bone mass appear to be linked, hypercalciuria seems to be an important determinant of reduced bone density in this setting as well.

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