New therapeutic options for bone diseases

Kocijan, Roland; Haschka, Judith; Feurstein, Julia; Zwerina, Jochen

doi:10.1007/s10354-020-00810-w

Cited by 5 publications

(7 citation statements)

References 51 publications

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“…Sclerostin inhibits osteoblast differentiation and, consequently, bone mineralization by interacting with the Wnt/β-catenin pathway, which represents one of the fundamental mechanisms of signaling that promotes cell proliferation, cell polarity and osteogenesis in humans [ 42 ]. Loss-of-function mutations in the SOST gene are associated with high bone mass [ 43 ], and the sclerostin antibody Romosozumab is a recently approved drug for the therapy of postmenopausal osteoporosis [ 44 ]. Additionally, a study by Shu Ma et al showed that microRNA-96, which is capable of binding and inactivating sclerostin, led to the Wnt signaling pathway activation with subsequent osteoblast differentiation in mice; vice versa, inhibition of miR-96 resulted in the suppression of bone formation [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Circulating SIRT1 and Sclerostin Correlates with Bone Status in Young Women with Different Degrees of Adiposity

et al. 2022

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Sirtuin1 (SIRT1) and sclerostin play important roles in adipose tissue and bone metabolism. We evaluated the circulating SIRT1 and sclerostin relationship with mass and quality of bone while considering the degree of adiposity. Sixty-six premenopausal women (16 underweight, 25 normal weight and 25 with obesity), aged <50 years, were enrolled. Plasma SIRT1, sclerostin and DXA body composition (total fat mass (FM), abdominal visceral adipose tissue, lean mass, trabecular bone score (TBS) and lumbar spine and femoral neck (FN) bone mineral density (BMD)) were assessed. The patients with obesity showed the lowest SIRT1 and TBS values and the highest sclerostin concentrations; BMD increased with FM and BMI and had an inverse association with SIRT1. Sclerostin was negatively correlated with SIRT1 (ρ = −0.37, p = 0.002). When spine BMD, FN BMD and TBS were standardized for BMI, a positive correlation with SIRT1 and a negative correlation with sclerostin were seen (p < 0.005). In the regression analysis, sclerostin was the best independent, negative predictor for BMD and TBS, while SIRT1 directly predicted TBS (p < 0.05). In conclusion, blood measurement of SIRT1 and sclerostin could represent a snapshot of the bone status that, taking into account the degree of adiposity, may reduce the interference of confounding factors in the interpretation of bone health parameters.

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Section: Discussionmentioning

confidence: 99%

Circulating SIRT1 and Sclerostin Correlates with Bone Status in Young Women with Different Degrees of Adiposity

et al. 2022

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“…Enthesopathies, arthropathies, fractures and pseudofractures cause chronic pain in adult patients and reduce their quality of life. Other symptoms may include dental complications, such as recurrent root abscesses, and hearing loss [1,8,9]. A patient with rickets/osteomalacia, chronic hypophosphatemia and elevated serum FGF23 levels raises the suspicion of XLH, even without positive family history or genetic testing [1].…”

Section: X-linked Hypophosphatemia (Xlh)mentioning

confidence: 99%

“…The approval of FDA regarding TIO treatment followed in June 2020. To date, the published consensus statement from Haffner et al [37], provides key recommendations for burosumab clinical use [8,18,37]. Regarding children and adolescents, burosumab treatment should be considered in XLH patients aged older than 6 months, who are not candidates or do not respond for any reason to conventional treatment or have complications related to conventional therapy.…”

Section: Burosumabmentioning

confidence: 99%

“…The inhibitory role of PPi in mineralization along with the role of PLP as a cofactor for many enzymatic procedures explain the musculoskeletal and systemic features of the disorder. The predominant manifestations of the disease consist of impaired bone mineralization, deformities, fractures, delayed fracture healing, premature tooth loss, muscle weakness and musculoskeletal pain [8]. Other non-bone specific manifestations include pulmonary abnormalities, seizures, impaired motor skills and nephrocalcinosis [46].…”

Section: Hypophosphatasia (Hpp)mentioning

confidence: 99%

“…Patients treated with phosphate and vitamin D supplements showed less hypomineralized periosteocytic lesions in bone biopsy 13 . Although supportive therapy helps reducing pain, improves fracture healing and dental disease, no benefit was observed regarding enthesopathies 1 8 . In another study, conventional therapy failed to achieve a normal height in patients with XLH, when compared to healthy control group 2 .…”

Section: Introductionmentioning

confidence: 99%

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Novel Therapeutic Agents for Rare Diseases of Calcium and Phosphate Metabolism

et al. 2022

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The last decade has been revolutionary regarding the management of rare bone diseases caused by impaired calcium and phosphate metabolism. Elucidation of the underlying genetic basis and pathophysiologic alterations has been the determinant factor for the development of new, disease-specific treatment agents. The phosphaturic hormone Fibroblast Growth Factor 23 (FGF23) possesses a critical role in the pathogenesis of various hypophosphatemic disorders. Among them, the genetic disorder of X-linked hypophosphatemia and the acquired syndrome of tumor-induced osteomalacia, although very rare, have attracted the scientific community’s attention towards designing an FGF23-inhibitor as a potential specific therapy. The monoclonal antibody burosumab was approved for the treatment of children and adult patients with X-linked hypophosphatemia and recently for tumor-induced osteomalacia patients, demonstrating benefits regarding their symptoms, biochemical profile and bone mineralization status. Asfotase alfa is a hydroxyapatite-targeted recombinant alkaline phosphatase, an enzymatic replacement therapy, substituting the defective activity of tissue non-specific alkaline phosphatase, in patients suffering from hypophosphatasia. Promising data regarding its favorable effect on survival rate, bone quality, fracture healing, muscle strength, mobility, respiratory function, and general quality of life have led to the approval of the drug for the treatment of childhood-onset hypophosphatasia. Given the high costs of treatment for both agents and their limited clinical use until now, more data are needed to define patients’ characteristics that make them ideal candidates for therapy. Long-term safety issues also need to be clarified.

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Osteoporosis in children and adolescents: how to treat and monitor?

et al. 2022

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Osteoporosis is a condition of increased bone fragility associated with fractures. Apart from primary genetic osteoporotic conditions, secondary osteoporosis in children is being increasingly recognized. As a result, there is growing interest in its prevention and treatment. Important goals of care are to prevent fractures, increase bone mass and trabecular and cortical thickness, reshape vertebral fractures, prevent (or correct) skeletal deformities, and improve mobility, independence, and quality of life. Secondary pediatric osteoporosis is often of multifactorial origin since affected children frequently have more than one acquired factor that is detrimental to bone health. Typical conditions causing osteoporosis are leukemias, progressive muscle or neurological disorders, as well as chronic inflammatory conditions and their treatment. Management of children with osteoporosis involves a multidisciplinary team involving pediatric experts from different subspecialties. With regard to prevention and early intervention, it is important to provide optimal management of any underlying systemic conditions including avoidance, or dose-reduction, of osteotoxic medications. Basic supporting life-style measures, such as appropriate nutrition, including adequate calcium intake and vitamin D, and physical activity are recommended, where possible. When pediatric treatment criteria for osteoporosis are met, antiresorptive drugs constitute the first pharmacological line treatment.Conclusion: This clinical review focuses on the prevention, treatment, and follow-up of children with, or at risk of developing, osteoporosis and the transition from pediatric to adult care. What is Known:• Osteoporosis and associated fractures can cause significant morbidity and reduce the quality of life.• The developing skeleton has huge potential for recovery and reshaping, thus early detection of fractures, assessment of recovery potential, and treatment of children with osteoporosis can prevent future fractures, deformities, and scoliosis, improve function and mobility, and reduce pain. What is New: • Osteoporosis in children and adolescents requires a multidisciplinary approach with a thorough assessment of recovery potential, and indication for therapy should be personalized. • Although bisphosphonates still represent the drug most commonly used to increase bone mass, improve mobility, and reduce pain and recurrence of fractures, new agents are being developed and could be beneficial in children with specific conditions.

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New therapeutic options for bone diseases

Cited by 5 publications

References 51 publications

Circulating SIRT1 and Sclerostin Correlates with Bone Status in Young Women with Different Degrees of Adiposity

Circulating SIRT1 and Sclerostin Correlates with Bone Status in Young Women with Different Degrees of Adiposity

Novel Therapeutic Agents for Rare Diseases of Calcium and Phosphate Metabolism

Osteoporosis in children and adolescents: how to treat and monitor?

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