Plasma periostin associates significantly with non-vertebral but not vertebral fractures in postmenopausal women: Clinical evidence for the different effects of periostin depending on the skeletal site

Kim, Beom Jun; Rhee, Yumie; Kim, Chong Hwa; Baek, Ki Hyun; Min, Yong Ki; Kim, Deog-Yoon; Ahn, Seong Hee; Kim, Hyeonmok; Lee, Seung Hun; Lee, Sun Young; Kang, Moo Il; Koh, Jung Min

doi:10.1016/j.bone.2015.08.014

Cited by 42 publications

(42 citation statements)

References 37 publications

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“…Similarly, markers of bone formation are systemically increased, whereas markers of bone resorption are unchanged in these patients, which reflects the status of the trabecular bone but not of cortical bone. In the future, high-resolution quantitative computed tomography and the development of cortical-bone markers, such as periostin, 36,37 may allow an assessment of these two bone compartments, as well as stratification of the two bone compartments with respect to risk prediction.…”

Section: Discussionmentioning

confidence: 99%

Cortical-Bone Fragility — Insights from sFRP4 Deficiency in Pyle’s Disease

et al. 2016

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BACKGROUND Cortical-bone fragility is a common feature in osteoporosis that is linked to nonvertebral fractures. Regulation of cortical-bone homeostasis has proved elusive. The study of genetic disorders of the skeleton can yield insights that fuel experimental therapeutic approaches to the treatment of rare disorders and common skeletal ailments. METHODS We evaluated four patients with Pyle’s disease, a genetic disorder that is characterized by cortical-bone thinning, limb deformity, and fractures; two patients were examined by means of exome sequencing, and two were examined by means of Sanger sequencing. After a candidate gene was identified, we generated a knockout mouse model that manifested the phenotype and studied the mechanisms responsible for altered bone architecture. RESULTS In all affected patients, we found biallelic truncating mutations in SFRP4, the gene encoding secreted frizzled-related protein 4, a soluble Wnt inhibitor. Mice deficient in Sfrp4, like persons with Pyle’s disease, have increased amounts of trabecular bone and unusually thin cortical bone, as a result of differential regulation of Wnt and bone morphogenetic protein (BMP) signaling in these two bone compartments. Treatment of Sfrp4-deficient mice with a soluble Bmp2 receptor (RAP-661) or with antibodies to sclerostin corrected the cortical-bone defect. CONCLUSIONS Our study showed that Pyle’s disease was caused by a deficiency of sFRP4, that cortical-bone and trabecular-bone homeostasis were governed by different mechanisms, and that sFRP4-mediated cross-regulation between Wnt and BMP signaling was critical for achieving proper cortical-bone thickness and stability. (Funded by the Swiss National Foundation and the National Institutes of Health.)

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Section: Discussionmentioning

confidence: 99%

Cortical-Bone Fragility — Insights from sFRP4 Deficiency in Pyle’s Disease

et al. 2016

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“…Two studies reported a weak positive association between periostin and osteoporotic fractures . Based on the mechanotransduction role of periostin, the authors hypothesized that subjects with low bone mass and poor microarchitecture may have higher mechanical strain in the remaining bone, resulting in increased periostin expression.…”

Section: Discussionmentioning

confidence: 99%

Serum Levels of a Cathepsin-K Generated Periostin Fragment Predict Incident Low-Trauma Fractures in Postmenopausal Women Independently of BMD and FRAX

Bonnet

Chevalley

Rizzoli

et al. 2017

Journal of Bone and Mineral Research

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Periostin is a matricellular protein involved in bone formation and bone matrix organization, but it is also produced by other tissues. Its circulating levels have been weakly associated with bone microstructure and prevalent fractures, possibly because periostin measured by the current commercial assays does not specifically reflect bone metabolism. In this context, we developed a new ELISA for a periostin fragment resulting from cathepsin K digestion (K-Postn). We hypothesized that circulating K-Postn levels could be associated with bone fragility. A total of 695 women (age 65.0 ± 1.5 years), enrolled in the Geneva Retirees Cohort (GERICO), were prospectively evaluated over 4.7 ± 1.9 years for the occurrence of low-trauma fractures. At baseline, we measured serum periostin, K-Postn, and bone turnover markers (BTMs), distal radius and tibia microstructure by HR-pQCT, hip and lumbar spine aBMD by DXA, and estimated fracture probability using the Fracture Risk Assessment Tool (FRAX). Sixty-six women sustained a low-trauma clinical fracture during the follow-up. Total periostin was not associated with fractures (HR [95% CI] per SD: 1.19 [0.89 to 1.59], p = 0.24). In contrast, K-Postn was significantly higher in the fracture versus nonfracture group (57.5 ± 36.6 ng/mL versus 42.5 ± 23.4 ng/mL, p < 0.001) and associated with fracture risk (HR [95%CI] per SD: 2.14 [1.54 to 2.97], p < 0.001). After adjustment for aBMD, FRAX, bone microstructure, or BTMs, K-Postn remained significantly associated with fracture risk. The performance of the fracture prediction models was improved by adding K-Postn to aBMD or FRAX (Harrell C index for fracture: 0.70 for aBMD + K-Post versus 0.58 for aBMD alone, p = 0.001; 0.73 for FRAX + K-Postn versus 0.65 for FRAX alone, p = 0.005). Circulating K-Postn predicts incident fractures independently of BMD, BTMs, and FRAX in postmenopausal women. Hence measurement of a periostin fragment resulting from in vivo cathepsin K digestion may help to identify subjects at high risk of fracture. © 2017 American Society for Bone and Mineral Research.

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“…One possible explanation is that periostin also correlates with bone repair that it is probably more pronounced in patients with fractures compared with all other patients. In postmenopausal status, there was no difference in circulating periostin levels between women with low and normal bone mass, 19 whereas periostin could predict for fractures 7 or it was elevated in patients with fractures. 8 Furthermore, the presence of different periostin isoforms with unknown activity on bone remodeling may also explain these differences.…”

Section: Discussionmentioning

confidence: 91%

“…This result is in accordance with data that high serum periostin levels are independently associated with increased fracture risk in postmenopausal women. 7, 8 Moreover, periostin is elevated in the serum of patients with different subtypes of hemoglobinopathies, disorders that also correlate with bone loss. 18 It is of interest that NDMM patients with fractures had markedly elevated bone marrow plasma periostin even compared with patients with high number of osteolytic lesions.…”

Section: Discussionmentioning

confidence: 99%

“…5 The significance of periostin on bone biology becomes evident by its influence on bone loss in several bone disorders. High serum periostin is independently associated with increased fracture risk in postmenopausal women, 6, 7 whereas high periostin has been associated with disease activity, systemic inflammation and bone damage in ankylosing spondylitis. 8 Periostin expression is upregulated by several members of the transforming growth factor-β superfamily, including activin-A, which has been found to be elevated in MM by our group.…”

Section: Introductionmentioning

confidence: 99%

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High levels of periostin correlate with increased fracture rate, diffuse MRI pattern, abnormal bone remodeling and advanced disease stage in patients with newly diagnosed symptomatic multiple myeloma

Terpos

Christoulas

Kastritis

et al. 2016

Blood Cancer Journal

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Periostin is an extracellular matrix protein that is implicated in the biology of normal bone remodeling and in different cancer cell growth and metastasis. However, there is no information on the role of periostin in multiple myeloma (MM). Thus, we evaluated periostin in six myeloma cell lines in vitro; in the bone marrow plasma and serum of 105 newly diagnosed symptomatic MM (NDMM) patients and in the serum of 23 monoclonal gammopathy of undetermined significance (MGUS), 33 smoldering MM (SMM) patients, 30 patients at the plateau phase post-first-line therapy, 30 patients at first relapse and 30 healthy controls. We found high levels of periostin in the supernatants of myeloma cell lines compared with ovarian cancer cell lines that were not influenced by the incubation with the stromal cell line HS5. In NDMM patients the bone marrow plasma periostin was almost fourfold higher compared with the serum levels of periostin and correlated with the presence of fractures and of diffuse magnetic resonance imaging pattern of marrow infiltration. Serum periostin was elevated in NDMM patients compared with healthy controls, MGUS and SMM patients and correlated with advanced disease stage, high lactate dehydrogenase, increased activin-A, increased bone resorption and reduced bone formation. Patients at first relapse had also elevated periostin compared with healthy controls, MGUS and SMM patients, while even patients at the plateau phase had elevated serum periostin compared with healthy controls. These results support an important role of periostin in the biology of myeloma and reveal periostin as a possible target for the development of antimyeloma drugs.

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Plasma periostin associates significantly with non-vertebral but not vertebral fractures in postmenopausal women: Clinical evidence for the different effects of periostin depending on the skeletal site

Cited by 42 publications

References 37 publications

Cortical-Bone Fragility — Insights from sFRP4 Deficiency in Pyle’s Disease

Cortical-Bone Fragility — Insights from sFRP4 Deficiency in Pyle’s Disease

Serum Levels of a Cathepsin-K Generated Periostin Fragment Predict Incident Low-Trauma Fractures in Postmenopausal Women Independently of BMD and FRAX

High levels of periostin correlate with increased fracture rate, diffuse MRI pattern, abnormal bone remodeling and advanced disease stage in patients with newly diagnosed symptomatic multiple myeloma

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