Organic nitrates for osteoporosis: an update

Hamilton, Celeste J.; Reid, Lauren S; Jamal, Sophie A.

doi:10.1038/bonekey.2012.259

Cited by 10 publications

(12 citation statements)

References 51 publications

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“…Although we were able to adjust for urbanization, there is a potential for many other confounders including, for example, seasonal differences in the prevalence of indoor and outdoor fractures, diet, education, employment or socioeconomic status. In addition, sunlight exposure might affect skeletal metabolism independently of vitamin D, for example, through dermal release of nitrite that, in turn may affect skeletal metabolism . There are also several problems in the use of register studies.…”

Section: Discussionmentioning

confidence: 99%

“…(66) These observations need to be considered alongside studies that have shown no seasonality in hip fracture rates. (67)(68)(69)(70)(71)(72)(73)(74) Thus, the effect size (the % difference between peak and trough values) varies markedly ranging from 0% to 30%. (52,61) In the present study, the effect size was 37.5% in men and 23.5% in women.…”

Section: Seasonal Variationmentioning

confidence: 99%

“…In addition, sunlight exposure might affect skeletal metabolism independently of vitamin D, for example, through dermal release of nitrite (73) that, in turn may affect skeletal metabolism. (74) There are also several problems in the use of register studies. Different identification algorithms applied to register studies will yield different results (75) sometimes with opposing conclusions on incidence.…”

Section: Strengths and Limitationsmentioning

confidence: 99%

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The Effect of Latitude on the Risk and Seasonal Variation in Hip Fracture in Sweden

Odén

Kanis

McCloskey

et al. 2014

Journal of Bone and Mineral Research

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Although the optimal requirement of vitamin D for skeletal health in the general community is controversial, vitamin D deficiency impairs bone mineralization and increases bone turnover via secondary hyperparathyroidism, thus accelerating bone loss and increasing fracture risk. Support for a role of vitamin D deficiency in the epidemiology of hip fracture is found in the seasonal variation of hip fracture incidence that is reported in several studies. If the association were causal, then the incidence and amplitude of the seasonal variation in hip fracture risk should vary by latitude. We addressed this hypothesis by examining the incidence of hip fracture in men and women aged 50 years or more from Sweden (latitudes 55 to 69°) between 1987 and 2009. In order to reduce double counting, only one fracture in a period of a year was counted per individual. Men contributed 104,888 fractures in 33,313,065 person years and women 264,362 fractures in 38,387,660 person years. The effects of season and latitude were examined by Poisson regression. As expected, hip fracture rates were higher in women than in men. After adjustment for age, season and population density, hip fracture incidence increased by 3.0% (95% CI: 2.7-3.2%) per degree increase in latitude for men and by 1.9% (95% CI: 1.8-2.1%) for women. There was a marked seasonal variation of hip fracture with the highest risk in February and lower by 37.5% in men and by 23.5% women during the summer. There were significant interactions of amplitude of the seasonal variation with latitude (p < 0.001 for both men and women), indicating that seasonal variation during the year was more pronounced in the north of Sweden than in the south. The associations found with latitude and season is consistent with a role of vitamin D in hip fracture causation.

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Section: Discussionmentioning

confidence: 99%

Section: Seasonal Variationmentioning

confidence: 99%

Section: Strengths and Limitationsmentioning

confidence: 99%

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The Effect of Latitude on the Risk and Seasonal Variation in Hip Fracture in Sweden

Odén

Kanis

McCloskey

et al. 2014

Journal of Bone and Mineral Research

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“…Though the exact mechanism of NO action is still unclear, it is believed that nitric oxide induces local vasodilation of arteries. Additionally, nitric oxide activates G‐protein‐linked mechanoreceptors in osteocytes to form or resorb bone and inhibits sclerostin and Wnt pathway …”

Section: Novel Targetsmentioning

confidence: 99%

“…Osteoblasts and osteocytes cells produce nitric oxide through nitric oxide synthase, which is reported to regulate osteoclast activity via RANKL/OPG pathway. 197 The high level of nitric oxide encourages the OPG production, which binds to RANK and reduces osteoclastogenesis. Simultaneously, it also inhibits sclerostin, which is known to antagonize osteoblast differentiation by suppression of the Wnt pathway.…”

Section: Nitratesmentioning

confidence: 99%

The underlying pathophysiology and therapeutic approaches for osteoporosis

Awasthi

Mani

Singh

et al. 2018

Medicinal Research Reviews

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With an increase in the ageing population worldwide, the prevalence of osteoporosis increases at an alarming rate in both male and female irrespective of their ethnicity. At present, the currently available therapeutic options are mostly limited to either bone resorptive or bone forming efficacies and both approaches are associated with serious side effects. Despite these options, there is still need for newer therapeutics to treat osteoporosis, which can offer beneficial effects for maintaining balanced dynamics between bone formation and bone resorption, devoid of any side effect. The proper understanding of pathophysiology of the disease is essential for designing or investigating an effective and safe anti-osteoporotic agent. This review represents a discussion around the molecular targets with their implications in disease progression, available therapeutic options, the emerging targets, and the importance of designing an effective anti-osteoporotic agent.

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A Novel, Direct NO Donor Regulates Osteoblast and Osteoclast Functions and Increases Bone Mass in Ovariectomized Mice

Kalyanaraman

Ramdani

Joshua

et al. 2016

Journal of Bone and Mineral Research

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Most FDA-approved treatments for osteoporosis target osteoclastic bone resorption. Only PTH derivatives improve bone formation, but they have drawbacks, and novel bone-anabolic agents are needed. Nitrates, which generate NO, improved BMD in estrogen-deficient rats and may improve bone formation markers and BMD in post-menopausal women. However, nitrates are limited by induction of oxidative stress and development of tolerance, and may increase cardiovascular mortality after long-term use. Here we studied nitrosyl-cobinamide (NO-Cbi), a novel, direct NO-releasing agent, in a mouse model of estrogen deficiency-induced osteoporosis. In murine primary osteoblasts, NO-Cbi increased intracellular cGMP, Wnt/β-catenin signaling, proliferation, and osteoblastic gene expression, and protected cells from apoptosis. Correspondingly, in intact and ovariectomized (OVX) female C57Bl/6 mice, NO-Cbi increased serum cGMP concentrations, bone formation, and osteoblastic gene expression, and in OVX mice, it prevented osteocyte apoptosis. NO-Cbi reduced osteoclasts in intact mice and prevented the known increase in osteoclasts in OVX mice, partially through a reduction in the RANKL/osteoprotegerin gene expression ratio, which regulates osteoclast differentiation, and partially through direct inhibition of osteoclast differentiation, observed in vitro in the presence of excess RANKL. The positive NO effects in osteoblasts were mediated by cGMP/PKG, but some of the osteoclast-inhibitory effects appeared to be cGMP-independent. NO-Cbi increased trabecular bone mass in both intact and OVX mice, consistent with its in vitro effects on osteoblasts and osteoclasts. NO-Cbi is a novel direct NO-releasing agent that, in contrast to nitrates, does not generate oxygen radicals, and combines anabolic and anti-resorptive effects in bone, making it an excellent candidate for treating osteoporosis.

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Organic nitrates for osteoporosis: an update

Cited by 10 publications

References 51 publications

The Effect of Latitude on the Risk and Seasonal Variation in Hip Fracture in Sweden

The Effect of Latitude on the Risk and Seasonal Variation in Hip Fracture in Sweden

The underlying pathophysiology and therapeutic approaches for osteoporosis

A Novel, Direct NO Donor Regulates Osteoblast and Osteoclast Functions and Increases Bone Mass in Ovariectomized Mice

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