Losartan

Losartan may or may not affect height growth as occassionally suppresion of osteoclasts decreases height growth.

Losartan increases bone mass and accelerates chondrocyte hypertrophy in developing skeleton.

“Angiotensin receptor blockers (ARBs) are a group of anti-hypertensive drugs that are widely used to treat pediatric hypertension. ARBs treat diseases such as Marfan syndrome or Alport syndrome has shown positive outcomes in animal and human studies, suggesting a broader therapeutic potential for this class of drugs. ¬†ARBs [effect] adult bone homeostasis; however, its effect on the growing skeleton in children is unknown. We investigated the effect of Losartan, an ARB, in regulating bone mass and cartilage during development in mice. Wild type mice were treated with Losartan from birth until 6weeks of age, after which bones were collected for microCT and histomorphometric analyses. Losartan increased trabecular bone volume vs. tissue volume (a 98% increase) and cortical thickness (a 9% increase) in 6-weeks old wild type mice. The bone changes were attributed to decreased osteoclastogenesis as demonstrated by reduced osteoclast number per bone surface in vivo and suppressed osteoclast differentiation in vitro. At the molecular level, Angiotensin II-induced ERK1/2 phosphorylation in RAW cells was attenuated by Losartan. RANKL-induced ERK1/2 phosphorylation was suppressed by Losartan, suggesting a convergence of RANKL and angiotensin signaling at the level of ERK1/2 regulation. To assess the effect of Losartan on cartilage development, we examined the cartilage phenotype of wild type mice treated with Losartan in utero from conception to 1day of age. Growth plates of these mice showed an elongated hypertrophic chondrocyte zone and increased Col10a1 expression level, with minimal changes in chondrocyte proliferation. Inhibition of the angiotensin pathway by Losartan increases bone mass and accelerates chondrocyte hypertrophy in growth plate during skeletal development.”

The images suggest that Losartan makes bones less porous.

“The growth plate is divided into four discrete zones defined by morphology: 1) the small round chondrocytes at the end of long bone constitute resting zone (RZ); 2) flattened chondrocytes with a typical columnar organization constitute proliferative zone (PZ); 3) the enlarged post-mitotic chondrocytes form the hypertrophic zone (HPZ); 4) the transitioning cells between proliferative and hypertrophic chondrocytes are referred to as pre-hypertrophic chondrocytes. Prominent Agtr1 signal in the hypertrophic chondrocytes (HPZ) ”

“Proliferative chondrocytes express a lower level of Agtr1 than hypertrophic chondrocytes do, while resting chondrocytes exhibit nearly absence of Agtr1expression”

“To evaluate how AngII signaling inhibition affects cartilage development in the long bone, we analyzed the growth plate of mice with or without Losartan treatment in utero from conception until P1. The total length of the growth plate did not show a significant difference between treated and untreated mice”

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