Theophylline, a methylxanthine drug induces osteopenia and alters calciotropic hormones, and prophylactic vitamin D treatment protects against these changes in rats

Pal, Subhashis; Khan, Kainat; China, Shyamsundar Pal; Mittal, Monika; Porwal, Konica; Shrivastava, Rahul; Taneja, Isha; Hossain, Zakir; Mandalapu, Dhanaraju; Gayen, Jiaur R.; Wahajuddin, Muhammad; Sharma, Vishnu L.; Trivedi, Arun Kumar; Sanyal, Sabyasachi; Bhadauria, Smrati; Godbole, Madan M.; Gupta, Sushil K.; Chattopadhyay, Naibedya

doi:10.1016/j.taap.2016.02.002

Cited by 32 publications

(23 citation statements)

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“…These results have shown the promotional effects of theophylline on skeletal calcium loss and its acceleration of the development of human osteopenia (34). The same conclusion regarding the detrimental effect of theophylline on bone loss was reported in another study (35).…”

Section: Discussionsupporting

confidence: 77%

Assessing the Associations of Blood Metabolites With Osteoporosis: A Mendelian Randomization Study

Liu

Wen

Zhang

et al. 2018

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context: Osteoporosis is a metabolic bone disease. The effect of blood metabolites on the development of osteoporosis remains elusive.Objective: To explore the relationship between blood metabolites and osteoporosis.Design and Methods: We used 2286 unrelated white subjects for the discovery samples and 3143 unrelated white subjects from the Framingham Heart Study (FHS) for the replication samples. The bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry. Genome-wide single nucleotide polymorphism (SNP) genotyping was performed using Affymetrix Human SNP Array 6.0 (for discovery samples) and Affymetrix SNP 500K and 50K array (for FHS replication samples). The SNP sets significantly associated with blood metabolites were obtained from a reported whole-genome sequencing study. For each subject, the genetic risk score of the metabolite was calculated from the genotype data of the metabolite-associated SNP sets. Pearson correlation analysis was conducted to evaluate the potential effect of blood metabolites on the variations in bone phenotypes; 10,000 permutations were conducted to calculate the empirical P value and false discovery rate.Results: We analyzed 481 blood metabolites. We identified multiple blood metabolites associated with hip BMD, such as 1,5-anhydroglucitol (P discovery , 0.0001; P replication = 0.0361), inosine (P discovery = 0.0018; P replication = 0.0256), theophylline (P discovery = 0.0048; P replication = 0.0433, gamma-glutamyl methionine (P discovery = 0.0047; P replication = 0.0471), 1-linoleoyl-2-arachidonoyl-GPC (18:2/20:4n6; P discovery = 0.0018; P replication = 0.0390), and X-12127 (P discovery = 0.0002; P replication = 0.0249). Conclusions:Our results suggest a modest effect of blood metabolites on the variations of BMD and identified several candidate blood metabolites for osteoporosis. (J Clin Endocrinol Metab 103: 1850-1855 O steoporosis is a metabolic bone disease, characterized as low bone mass and increased bone fragility. It has been reported that currently .40 million people are at risk of bone fractures, and the incidence of osteoporotic fractures is increasing rapidly in the United States (1). Bone mineral density (BMD) is commonly used to 1850https://academic.oup.com/jcem

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Section: Discussionsupporting

confidence: 77%

Assessing the Associations of Blood Metabolites With Osteoporosis: A Mendelian Randomization Study

Liu

Wen

Zhang

et al. 2018

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…Though the mechanisms have not been clearly understood, in vitro studies suggest a possible mechanism for VDR-cancer growth inhibition by stimulating apoptosis [ 89 ]. In a remarkable study it has been found that 1, 25 D3 protected osteoblasts from theophylline induced apoptosis and also reduces oxidative stress [ 90 ].…”

Section: Vitamin D Analogsmentioning

confidence: 99%

Current therapies in alleviating liver disorders and cancers with a special focus on the potential of vitamin D

et al. 2018

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BackgroundLiver dysfunction is a topic of global concern with many advancing therapies being researched. Though vitamin D takes a center place, other therapies especially nutritional are also gaining ground. Vitamin D has gone beyond its role in skeletal disorders by showcasing its associations in other metabolic dysfunctions too.ResultEpidemiological evidences show a correlation between the status of vitamin D and different forms of cancer. Vitamin D receptors and alterations in gene expression appear decisive in the development of chronic liver disorders. Nutritional status therefore plays a significant role in avoiding the complications related to liver dysfunctions, making it mandatory in maintaining vitamin D sufficiency in the body. Therapies with omega-3 fatty acids, antioxidants, amino acids, steroids also render benefits which could be further explored. Recent research on the progression of certain forms of liver cancer using vitamin D analogs like Seocalcitol EB 1089 has shown good promise.ConclusionThe anti-inflammatory and immuno- regulatory properties of vitamin D makes its analogs, suitable candidates of better choice for the prevention and treatment of liver disorders and cancer.

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“…In addition, substantive numbers of cellular and basic studies conducted over the years do not negate a role for vitamin D in bone remodeling, fracture healing or prevention or both, although there seems to be a possible bi phasic dose-related response, differing rates of Vitamin D2 and D3 clearance [96] , differing vitamin D supplementation needs [96] and inter-species differences. As well, vitamin D may not only be osteo-protective in some cases [97,98] , but potentially relevant in exerting optimal fracture repair [94] , direct effects on both osteoblasts as well as osteoclasts [99] , and bone formation [96] , as well helpful for purposes of fracture prevention [100] , falls prevention [96] , and attenuating new fracture occurrence rates [101] .…”

Section: Discussionmentioning

confidence: 99%

Vitamin D and Fracture Healing: An Ongoing Puzzle

Marks

2019

International Journal of Orthopaedics

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Despite a large period of time, very few studies covering the present topic can be considered to answer the review questions effectively, and among those that prevail, no conclusive evidence regarding the routine use of vitamin D as a supplement in cases with bone fractures and their prevention has emerged. CONCLUSION: More research regarding a role for vitamin D in bone fracture healing and prevention is warranted.

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Theophylline, a methylxanthine drug induces osteopenia and alters calciotropic hormones, and prophylactic vitamin D treatment protects against these changes in rats

Cited by 32 publications

References 31 publications

Assessing the Associations of Blood Metabolites With Osteoporosis: A Mendelian Randomization Study

Assessing the Associations of Blood Metabolites With Osteoporosis: A Mendelian Randomization Study

Current therapies in alleviating liver disorders and cancers with a special focus on the potential of vitamin D

Vitamin D and Fracture Healing: An Ongoing Puzzle

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