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Osteoporosis and Related Bone Metabolic Disease

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Endocrinology & Metabolism".

Deadline for manuscript submissions: closed (30 April 2021) | Viewed by 36279

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Prof. Dr. Heinrich Resch

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Academic Teaching Hospital of the University Vienna, School of Medicine, University Vienna, Stumpergasse 13, 1060 Vienna, Austria
Interests: bone quality; fracture assessment; miRNA

Special Issue Information

Dear Colleagues,

A large number of heterogeneous causes (e.g., metabolic, inflammatory, autoimmune, vascular, renal diseases, and even drugs), collectively grouped as secondary causes of osteoporosis, may lead to bone loss or damage of architecture through a number of mechanisms. Although these secondary causes of osteoporosis are the most frequently observed causes of unexpected bone loss, they can only be diagnosed by a high degree of suspicion and clinical experience, performing the appropriate investigations. In inflammatory disorders like rheumatoid arthritis or chronic inflammatory bowel diseases, but also vascular diseases, T-cell activation and consequently pro-inflammatory cascades trigger the increased expression of T-cell-derived RANKL. In addition, there is a new biomarker signature of bone-related miRNAs which is promising in certain clinical features. Glucocorticoids, often used to control disease activity, decrease the osteoblasts in number and function and additionally inhibit OPG expression. The ubiquitous occurrence of disease-related secondary changes in bone metabolism implies that numerous medical disciplines need to interact. Screening for secondary causes of osteoporosis, and the search for new modes of action should present a substantial part in osteoporosis management. With this Special Issue, we hope to encourage submissions that discuss the current management of osteoporosis and related metabolic bone diseases.

Prof. Heinrich Resch
Guest Editor

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Keywords

Osteoporosis
Fractures
RANKL
miRNA
Bone quality
Bone mineral density
Bone strength

Published Papers (12 papers)

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Editorial

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3 pages, 191 KiB

Open AccessEditorial

Metabolic Bone Diseases—A Topic of Great Diversity

by Heinrich Resch, Afrodite Zendeli and Roland Kocijan

J. Clin. Med. 2022, 11(21), 6447; https://doi.org/10.3390/jcm11216447 - 31 Oct 2022

Cited by 1 | Viewed by 998

Abstract

The progress in research has improved the understanding of the epidemiology and pathogenesis of osteoporosis and bone disorders in general [...] Full article

(This article belongs to the Special Issue Osteoporosis and Related Bone Metabolic Disease)

Research

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11 pages, 2189 KiB

Open AccessArticle

Timing of Bisphosphonate (Alendronate) Initiation after Surgery for Fragility Fracture: A Population-Based Cohort Study

by Meng-Huang Wu, Yu-Sheng Lin, Christopher Wu, Ching-Yu Lee, Yi-Chia Chen, Tsung-Jen Huang and Jur-Shan Cheng

J. Clin. Med. 2021, 10(12), 2541; https://doi.org/10.3390/jcm10122541 - 08 Jun 2021

Cited by 4 | Viewed by 2457

Abstract

Bisphosphonates are used as first-line treatment for the prevention of fragility fracture (FF); they act by inhibiting osteoclast-mediated bone resorption. The timing of their administration after FF surgery is controversial; thus, we compared the incidence of second FF, surgery for second FF, and adverse events associated with early initiation of bisphosphonates (EIBP, within 3 months of FF surgery) and late initiation of bisphosphonates (LIBP, 3 months after FF surgery) in bisphosphonate-naïve patients. This retrospective population-based cohort study used data from Taiwan’s Health and Welfare Data Science Center (2004–2012). A total of 298,377 patients received surgeries for FF between 2006 and 2010; of them, 1209 (937 EIBP and 272 LIBP) received first-time bisphosphonates (oral alendronate, 70 mg, once a week). The incidence of second FF (subdistribution hazard ratio (SHR) = 0.509; 95% confidence interval (CI): 0.352–0.735), second FF surgery (SHR = 0.452; 95% CI: 0.268–0.763), and adverse events (SHR = 0.728; 95% CI: 0.594–0.893) was significantly lower in the EIBP group than in the LIBP group. Our findings indicate that bisphosphonates should be initiated within 3 months after surgery for FF. Full article

(This article belongs to the Special Issue Osteoporosis and Related Bone Metabolic Disease)

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14 pages, 2967 KiB

Open AccessArticle

TRAP5b and RANKL/OPG Predict Bone Pathology in Patients with Gaucher Disease

by Margarita Ivanova, Julia Dao, Lauren Noll, Jacqueline Fikry and Ozlem Goker-Alpan

J. Clin. Med. 2021, 10(10), 2217; https://doi.org/10.3390/jcm10102217 - 20 May 2021

Cited by 9 | Viewed by 3236

Abstract

Background and objective: Bone involvement occurs in 75% of patients with Gaucher disease (GD), and comprises structural changes, debilitating pain, and bone density abnormalities. Osteoporosis is a silent manifestation of GD until a pathologic fracture occurs. Thus, early diagnosis is crucial for identifying high-risk patients in order to prevent irreversible complications. Methods: Thirty-three patients with GD were assessed prospectively to identify predictive markers associated with bone density abnormalities, osteopenia (OSN), and osteoporosis (OSR). Subjects were categorized into three cohorts based on T- or Z-scores of bone mineral density (BMD). The first GD cohort consisted of those with no bone complications (Z-score ≥ −0.9; T-scores ≥ −1), the second was the OSN group (−1.8 ≥ Z-score ≥ −1; −2.5 ≥ T-score ≥ −1), and the third was the OSR group (Z-score ≤ −1.9; T-scores ≤ −2.5). Serum levels of TRAP5b, RANKL, OPG, and RANK were quantified by enzyme-linked immunosorbent assays. Results: TRAP5b levels were increased in GD patients, and showed a positive correlation with GD biomarkers, including plasma glucosylsphingosine (lyso-Gb1) and macrophage activation markers CCL18 and chitotriosidase. The highest level of TRAP5b was measured in patients with osteoporosis. The elevation of RANKL and RANKL/OPG ratio correlated with osteopenia in GD. Conclusion: TRAP5b, RANKL, and RANKL/OPG elevation indicate osteoclast activation in GD. TRAP5b is a potential bone biomarker for GD with the ability to predict the progression of bone density abnormalities. Full article

(This article belongs to the Special Issue Osteoporosis and Related Bone Metabolic Disease)

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10 pages, 576 KiB

Open AccessArticle

Bone Effect and Safety of One-Year Denosumab Therapy in a Cohort of Renal Transplanted Patients: An Observational Monocentric Study

by Carlo Alfieri, Valentina Binda, Silvia Malvica, Donata Cresseri, Mariarosaria Campise, Maria Teresa Gandolfo, Anna Regalia, Deborah Mattinzoli, Silvia Armelloni, Evaldo Favi, Paolo Molinari and Piergiorgio Messa

J. Clin. Med. 2021, 10(9), 1989; https://doi.org/10.3390/jcm10091989 - 06 May 2021

Cited by 7 | Viewed by 1867

Abstract

In 32-kidney transplanted patients (KTxps), the safety and the effects on BMD and mineral metabolism (MM) of one-year treatment with denosumab (DB) were studied. Femoral and vertebral BMD and T-score, FRAX score and vertebral fractures (sVF) before (T0) and after 12 months (T12) of treatment were measured. MM, renal parameters, hypocalcemic episodes (HpCa), urinary tract infections (UTI), major graft and KTxps outcomes were monitored. The cohort was composed mainly of females, n = 21. We had 29 KTxps on steroid therapy and 22 KTxps on vitamin D supplementation. At T0, 25 and 7 KTxps had femoral osteoporosis (F-OPS) and osteopenia (F-OPS), respectively. Twenty-three and six KTxps had vertebral osteoporosis (V-OPS) and osteopenia (V-OPS), respectively. Seventeen KTxps had sVF. At T12, T-score increased at femoral and vertebral sites (p = 0.05, p = 0.008). The prevalence of F-OPS and V-OPS reduced from 78% to 69% and from 72% to 50%, respectively. Twenty-five KTxps ameliorated FRAX score and two KTxps had novel sVF. At T12, a slight reduction of Ca was present, without HpCa. Four KTxps had UTI. No graft rejections, loss of graft or deaths were reported. Our preliminary results show a good efficacy and safety of DB in KTxps. Longer and randomized studies involving more KTxps might elucidate the possible primary role of DB in the treatment of bone disorders in KTxps. Full article

(This article belongs to the Special Issue Osteoporosis and Related Bone Metabolic Disease)

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10 pages, 862 KiB

Open AccessArticle

High Cortico-Trabecular Transitional Zone Porosity and Reduced Trabecular Density in Men and Women with Stress Fractures

by Afrodite Zendeli, Minh Bui, Lukas Fischer, Ali Ghasem-Zadeh, Wolfgang Schima and Ego Seeman

J. Clin. Med. 2021, 10(5), 1123; https://doi.org/10.3390/jcm10051123 - 08 Mar 2021

Cited by 3 | Viewed by 1934

Abstract

To determine whether stress fractures are associated with bone microstructural deterioration we quantified distal radial and the unfractured distal tibia using high resolution peripheral quantitative computed tomography in 26 cases with lower limb stress fractures (15 males, 11 females; mean age 37.1 ± 3.1 years) and 62 age-matched healthy controls (24 males, 38 females; mean age 35.0 ± 1.6 years). Relative to controls, in men, at the distal radius, cases had smaller cortical cross sectional area (CSA) (p = 0.012), higher porosity of the outer transitional zone (OTZ) (p = 0.006), inner transitional zone (ITZ) (p = 0.043) and the compact-appearing cortex (CC) (p = 0.023) while trabecular vBMD was lower (p = 0.002). At the distal tibia, cases also had a smaller cortical CSA (p = 0.008). Cortical porosity was not higher, but trabecular vBMD was lower (p = 0.001). Relative to controls, in women, cases had higher distal radial porosity of the OTZ (p = 0.028), ITZ (p = 0.030) not CC (p = 0.054). Trabecular vBMD was lower (p = 0.041). Distal tibial porosity was higher in the OTZ (p = 0.035), ITZ (p = 0.009), not CC. Stress fractures are associated with compromised cortical and trabecular microstructure. Full article

(This article belongs to the Special Issue Osteoporosis and Related Bone Metabolic Disease)

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11 pages, 1143 KiB

Open AccessArticle

Fragility Fractures and Imminent Fracture Risk in the Spanish Population: A Retrospective Observational Cohort Study

by Maria-José Montoya-García, Mercè Giner, Rodrigo Marcos, David García-Romero, Francisco-Jesús Olmo-Montes, Mª José Miranda, Blanca Hernández-Cruz, Miguel-Angel Colmenero and Mª Angeles Vázquez-Gámez

J. Clin. Med. 2021, 10(5), 1082; https://doi.org/10.3390/jcm10051082 - 05 Mar 2021

Cited by 9 | Viewed by 1781

Abstract

Fragility fractures constitute a major public health problem worldwide, causing important high morbidity and mortality rates. The aim was to present the epidemiology of fragility fractures and to assess the imminent risk of a subsequent fracture and mortality. This is a retrospective population-based cohort study (n = 1369) with a fragility fracture. We estimated the incidence rate of index fragility fractures and obtained information on the subsequent fractures and death during a follow-up of up to three years. We assessed the effect of age, sex, and skeletal site of index fracture as independent risk factors of further fractures and mortality. Incidence rate of index fragility fractures was 86.9/10,000 person-years, with highest rates for hip fractures in women aged ≥80 years. The risk of fracture was higher in subjects with a recent fracture (Relative Risk(RR), 1.80; p < 0.01). Higher age was an independent risk factor for further fracture events. Significant excess mortality was found in subjects aged ≥80 years and with a previous hip fracture (hazard ratio, 3.43 and 2.48, respectively). It is the first study in Spain to evaluate the incidence of major osteoporotic fractures, not only of the hip, and the rate of imminent fracture. Our results provide further evidence highlighting the need for early treatment. Full article

(This article belongs to the Special Issue Osteoporosis and Related Bone Metabolic Disease)

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15 pages, 713 KiB

Open AccessArticle

Fractal-Based Analysis of Bone Microstructure in Crohn’s Disease: A Pilot Study

by Judith Haschka, Daniel Arian Kraus, Martina Behanova, Stephanie Huber, Johann Bartko, Jakob E. Schanda, Philip Meier, Arian Bahrami, Shahin Zandieh, Jochen Zwerina and Roland Kocijan

J. Clin. Med. 2020, 9(12), 4116; https://doi.org/10.3390/jcm9124116 - 20 Dec 2020

Cited by 4 | Viewed by 2185

Abstract

Crohn’s disease (CD) is associated with bone loss and increased fracture risk. TX-Analyzer™ is a new fractal-based technique to evaluate bone microarchitecture based on conventional radiographs. The aim of the present study was to evaluate the TX-Analyzer™ of the thoracic and lumbar spine in CD patients and healthy controls (CO) and to correlate the parameters to standard imaging techniques. 39 CD patients and 39 age- and sex-matched CO were analyzed. Demographic parameters were comparable between CD and CO. Bone structure value (BSV), bone variance value (BVV) and bone entropy value (BEV) were measured at the vertebral bodies of T7 to L4 out of lateral radiographs. Bone mineral density (BMD) and trabecular bone score (TBS) by dual energy X-ray absorptiometry (DXA) were compared to TX parameters. BSV and BVV of the thoracic spine of CD were higher compared to controls, with no difference in BEV. Patients were further divided into subgroups according to the presence of a history of glucocorticoid treatment, disease duration > 15 years and bowel resection. BEV was significantly lower in CD patients with these prevalent risk factors, with no differences in BMD at all sites. Additionally, TBS was reduced in patients with a history of glucocorticoid treatment. Despite a not severely pronounced bone loss in this population, impaired bone quality in CD patients with well-known risk factors for systemic bone loss was assessed by TX-Analyzer™. Full article

(This article belongs to the Special Issue Osteoporosis and Related Bone Metabolic Disease)

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10 pages, 753 KiB

Open AccessArticle

Impact of Hormonal Replacement Therapy on Bone Mineral Density in Premature Ovarian Insufficiency Patients

by Agnieszka Podfigurna, Marzena Maciejewska-Jeske, Malgorzata Nadolna, Paula Mikolajska-Ptas, Anna Szeliga, Przemyslaw Bilinski, Paulina Napierala and Blazej Meczekalski

J. Clin. Med. 2020, 9(12), 3961; https://doi.org/10.3390/jcm9123961 - 07 Dec 2020

Cited by 14 | Viewed by 2170

Abstract

Premature ovarian insufficiency (POI) is a type of hypergonadotropic hypogonadism caused by impaired ovarian function before the age of 40. Due to the hypoestrogenism, women with POI experience a variety of health complications, including an increased risk of bone mineral density loss and developing osteopenia and osteoporosis, which poses an important problem for public health. Purpose: The aim of this study was to evaluate and compare the values of bone mineral density (BMD), T-score and Z-score within the lumbar spine (L1-L4) using the dual energy X-ray absorptiometry method. The dual-energy X-ray absorptiometry (DXA) scans described in this original prospective article were performed at the time of POI diagnosis and after treatment with sequential hormone replacement therapy (HRT). Materials and methods: This study included 132 patients with a mean age of 31.86 ± 7.75 years who had been diagnosed with idiopathic POI. The control group consisted of 17 healthy women with regular menstrual cycles, with a mean age of 23.21 ± 5.86 years. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17-estradiol (E2), prolactin (PRL), testosterone (T), dehydroepiandrosterone sulfate (DHEA-S), thyroid-stimulating hormone (TSH), free thyroxine (fT4), insulin, and fasting serum glucose were measured. Lumbar spine (L1-L4) BMD was assessed by means of dual-energy X-ray absorptiometry. DXA scans were performed at the time of diagnosis and following treatment with sequential hormone replacement therapy (HRT) comprised of daily oral 2 mg 17-β-estradiol and 10 mg dydrogesterone. The mean time of observation was 3 ± 2 years. Results: Patients in the POI group presented with characteristic hypergonadotropic hypogonadism. They had a significantly decreased mean lumbar spine BMD when compared to healthy controls (1.088 ± 0.14 g/cm²) vs. 1.150 ± 0.30 g/cm²) (p = 0.04) as well as a decreased T-score (0.75 ± 1.167 vs. −0.144 ± 0.82) (p = 003). There was a significant increase in BMD (1.088 ± 0.14 vs. 1.109 ± 0.14; p < 0.001), T-score (−0.75 ± 1.17 vs. −0.59 ± 1.22; p < 0.001), and Z-score (−0.75 ± 1.12 vs. −0.49 ± 1.11; p < 0.001) after the implementation of HRT when compared to pre-treatment results. Conclusions: In conclusion, this study has demonstrated that patients with POI often have decreased bone mineral density and that the implementation of HRT has a significant and positive influence on bone mass. The implementation of full-dose HRT and monitoring of bone status is particularly important in these patients. Full article

(This article belongs to the Special Issue Osteoporosis and Related Bone Metabolic Disease)

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13 pages, 958 KiB

Open AccessArticle

Metformin Attenuates Osteoporosis in Diabetic Patients with Carcinoma in Situ: A Nationwide, Retrospective, Matched-Cohort Study in Taiwan

by Chieh-Hua Lu, Chi-Hsiang Chung, Feng-Chih Kuo, Kuan-Chan Chen, Chia-Hao Chang, Chih-Chun Kuo, Chien-Hsing Lee, Sheng-Chiang Su, Jhih-Syuan Liu, Fu-Huang Lin, Chang-Huei Tsao, Po-Shiuan Hsieh, Yi-Jen Hung, Chang-Hsun Hsieh and Wu-Chien Chien

J. Clin. Med. 2020, 9(9), 2839; https://doi.org/10.3390/jcm9092839 - 02 Sep 2020

Cited by 10 | Viewed by 2204

Abstract

Patients with diabetes are at increased risk of cancer development and osteoporosis. Metformin is an effective agent for diabetes management. Epidemiological studies have identified an association between metformin use and cancer prevention. This article outlines the potential for metformin to attenuate the rate of osteoporosis in diabetic patients with carcinoma in situ (CIS). From the National Health Insurance Research Database of Taiwan, 7827 patients with diabetes with CIS who were receiving metformin therapy were selected, along with 23,481 patients as 1:3 sex-, age- and index year-matched controls, who were not receiving metformin therapy. A Cox proportional hazard analysis was used to compare the rate of osteoporosis during an average of 15-year follow-up. Of the subjects who were enrolled, 801 (2.56%) had osteoporosis, including 168 from the metformin group (2.15%) and 633 from the without metformin group (2.70%). The metformin group presented a lower rate of osteoporosis at the end of follow-up (p = 0.009). The Cox proportional hazard regression analysis revealed a lower rate of osteoporosis for the metformin group (adjusted hazard ratio of 0.820; 95% confidence interval = 0.691–0.972, p = 0.022). Diabetic patients with CIS under metformin therapy presented lower osteoporosis rate than those who were not receiving metformin therapy. Full article

(This article belongs to the Special Issue Osteoporosis and Related Bone Metabolic Disease)

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Review

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12 pages, 532 KiB

Open AccessReview

Testosterone and Bone Health in Men: A Narrative Review

by Kazuyoshi Shigehara, Kouji Izumi, Yoshifumi Kadono and Atsushi Mizokami

J. Clin. Med. 2021, 10(3), 530; https://doi.org/10.3390/jcm10030530 - 02 Feb 2021

Cited by 45 | Viewed by 6280

Abstract

Bone fracture due to osteoporosis is an important issue in decreasing the quality of life for elderly men in the current aging society. Thus, osteoporosis and bone fracture prevention is a clinical concern for many clinicians. Moreover, testosterone has an important role in maintaining bone mineral density (BMD) among men. Some testosterone molecular mechanisms on bone metabolism have been currently established by many experimental data. Concurrent with a decrease in testosterone with age, various clinical symptoms and signs associated with testosterone decline, including decreased BMD, are known to occur in elderly men. However, the relationship between testosterone levels and osteoporosis development has been conflicting in human epidemiological studies. Thus, testosterone replacement therapy (TRT) is a useful tool for managing clinical symptoms caused by hypogonadism. Many recent studies support the benefit of TRT on BMD, especially in hypogonadal men with osteopenia and osteoporosis, although a few studies failed to demonstrate its effects. However, no evidence supporting the hypothesis that TRT can prevent the incidence of bone fracture exists. Currently, TRT should be considered as one of the treatment options to improve hypogonadal symptoms and BMD simultaneously in symptomatic hypogonadal men with osteopenia. Full article

(This article belongs to the Special Issue Osteoporosis and Related Bone Metabolic Disease)

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27 pages, 3265 KiB

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Advances in Osteoporotic Bone Tissue Engineering

by Cosmin Iulian Codrea, Alexa-Maria Croitoru, Cosmin Constantin Baciu, Alina Melinescu, Denisa Ficai, Victor Fruth and Anton Ficai

J. Clin. Med. 2021, 10(2), 253; https://doi.org/10.3390/jcm10020253 - 12 Jan 2021

Cited by 39 | Viewed by 5598

Abstract

The increase in osteoporotic fracture worldwide is urging bone tissue engineering research to find new, improved solutions both for the biomaterials used in designing bone scaffolds and the anti-osteoporotic agents capable of promoting bone regeneration. This review aims to report on the latest advances in biomaterials by discussing the types of biomaterials and their properties, with a special emphasis on polymer-ceramic composites. The use of hydroxyapatite in combination with natural/synthetic polymers can take advantage of each of their components properties and has a great potential in bone tissue engineering, in general. A comparison between the benefits and potential limitations of different scaffold fabrication methods lead to a raised awareness of the challenges research face in dealing with osteoporotic fracture. Advances in 3D printing techniques are providing the ways to manufacture improved, complex, and specialized 3D scaffolds, capable of delivering therapeutic factors directly at the osteoporotic skeletal defect site with predefined rate which is essential in order to optimize the osteointegration/healing rate. Among these factors, strontium has the potential to increase osseointegration, osteogenesis, and healing rate. Strontium ranelate as well as other biological active agents are known to be effective in treating osteoporosis due to both anti-resorptive and anabolic properties but has adverse effects that can be reduced/avoided by local release from biomaterials. In this manner, incorporation of these agents in polymer-ceramic composites bone scaffolds can have significant clinical applications for the recovery of fractured osteoporotic bones limiting or removing the risks associated with systemic administration. Full article

(This article belongs to the Special Issue Osteoporosis and Related Bone Metabolic Disease)

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12 pages, 1458 KiB

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Bone Mineral Density, Osteoporosis, and Fracture Risk in Adult Patients with Psoriasis or Psoriatic Arthritis: A Systematic Review and Meta-Analysis of Observational Studies

by Tai-Li Chen, Jing-Wun Lu, Yu-Wen Huang, Jen-Hung Wang and Kuei-Ying Su

J. Clin. Med. 2020, 9(11), 3712; https://doi.org/10.3390/jcm9113712 - 19 Nov 2020

Cited by 20 | Viewed by 3873

Abstract

Introduction: Awareness of psoriasis-related comorbidities has been established in the current guidelines; however, evidence regarding the association of bone density or bone fragility with psoriatic disease remains inconclusive. Methods: We conducted a systematic review and meta-analysis to assess bone mineral density and the risk of osteoporosis and fractures in patients with psoriatic disease, including those with cutaneous psoriasis and psoriatic arthritis. We searched electronic databases for published observational studies. A meta-analysis was performed using the random-effect model. Pooled estimates and their confidence intervals (CIs) were calculated. Small-study effects were examined using the Doi plot and Luis Furuya–Kanamori index. Results: The analysis of the standardized mean difference in the absolute value of bone mineral density at different measuring sites (lumbar spine, femoral neck, and total hip) revealed no significant difference between patients with psoriatic disease and non-psoriatic controls. The pooled results of the adjusted odds ratios (ORs) demonstrated no increased risk of osteoporosis in patients with psoriatic disease. Notably, patients with psoriatic disease had a higher OR of developing bone fractures (adjusted OR: 1.09; 95% CI: 1.06 to 1.12; I²: 0%). Conclusion: Patients with psoriatic disease may be more likely to develop fractures compared with non-psoriatic controls. This higher risk for fracture may not necessarily be associated with lower bone mineral density nor a higher risk for osteoporosis. Full article

(This article belongs to the Special Issue Osteoporosis and Related Bone Metabolic Disease)

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