New guidance for MHT in postmenopausal women at risk of osteoporosis
News Review
11 OCTOBER 2024 ausdoc . com . au
The remarkable story of Dr Akira Endo ’ s statin revolution
New guidance for MHT in postmenopausal women at risk of osteoporosis
The Royal Australian College of General Practitioners ( RACGP ) in partnership with Healthy Bones Australia released new guidelines and positioning statements earlier this year on the management of osteoporosis and fracture prevention in postmenopausal women , stating : 1
“ Consider oestrogen replacement therapy to reduce the risk of fragility fractures in postmenopausal women within 10 years of menopause . The increased risk of adverse events associated with treatment should be carefully weighed against benefits .”*
* Please refer to the relevant Estrogen Replacement Therapy Product Information for indications and prescribing information .
Paul Smith and Megan Howe
How he made one of the most important drug discoveries since penicillin .
PHOTO : THE GAIRDNER FOUNDATION
“
I
WAS born into a rural farming family in northern Japan , in Akita , where I lived for 17 years with my extended family , including my grandparents .
“ My grandfather … was a great home teacher to me … and thanks to his influence , I became fascinated with mushrooms and other moulds .”
These are the words of Dr Akira Endo ( PhD ), looking back at his life in 2010 . The reference to “ mushrooms and other moulds ” is a clue to the reason why he can be credited with saving the lives of millions .
He died in June this year aged 90 , but he was the scientist who isolated three active metabolites from a culture broth of blue-green mould , one of which led to the first statin .
His background was humble . He finished high school in the early 1950s and entered Tohoku University ’ s College of Agriculture where he trained as a biochemist . After completing his doctorate , he joined a Japanese pharma company called Sankyo .
First success
His first professional success seems to be finding a grape-parasitic fungus that could produce an enzyme to hydrolyse viscid pectin contaminating wines and ciders .
But his interests evolved and he began reading about cholesterol biosynthesis in greater detail , eventually writing to the German-American biochemist Konrad Bloch , who had received the Nobel prize in 1964 on the mechanism and regulation of cholesterol and fatty acid metabolism .
The classes held by one of his scientific heroes were full , so he ended up at the Albert Einstein College of Medicine in New York .
It was while living in the city that Dr Endo noted the large number of elderly and overweight people .
“ In the residential area of the Bronx where I lived , there were many elderly couples living by themselves , and I often saw ambulances going to take an elderly person who had suffered a heart attack to the hospital .
“ At that time , coronary heart disease was the main cause of death in the US .
“ The number of patients with hypercholesterolaemia was said to exceed 10 million .”
A crucial breakthrough
It was only after
‘ We began using culture broths of thousands of fungi .’ his return to Tokyo in 1968 , however , that his work began to yield results .
He said although no metabolites that inhibited any enzymes involved in cholesterol synthesis had been isolated previously , he suspected that fungi-like moulds and mushrooms would produce antibiotics that inhibited HMG-CoA reductase , the enzyme for cholesterol synthesis .
“ Inspired by [ Sir Alexander ] Fleming ’ s success with moulds , we began our project using culture broths of thousands of fungi in April 1971 , and one year later , after 3800 strains of fungi , we found that a culture broth of mould showed potent inhibitory activity ,” he wrote .
This was a known substance — citrinin . But while scientists had found it could lower serum cholesterol levels in rats , it turned out further research had been suspended because of its toxicity to the kidneys .
But it was this rediscovery that according to Dr Endo gave “ us hope and courage that we might be able to discover much better active substances in the near future ”.
And that is what happened . In the summer of 1972 , he said they found a second active culture broth , Penicillium citrinum Pen- 51 , which they had isolated from a rice sample collected at a grain shop in Kyoto , Japan .
It was very similar to the blue-green mould that grows on overripe oranges and melons .
It then took a further year for his team to isolate the metabolites ( by solvent extraction , silica gel chromatography , and crystallisation ) which proved potent in inhibiting cholesterol synthesis .
The most active of the three was initially labelled ML-236B . It would later get the name compactin . It was the crucial breakthrough .
“ I had set my sights on finding a competitive inhibitor of HMG-CoA reductase , and compactin seemed to be a wonderful gift from nature ,” he said . In 1976 , his team published two papers on their discovery .
Unfortunately , when it PAGE 16
To access the guidelines and positioning statements , scan here
References : 1 . The Royal Australian College of General Practitioners . Osteoporosis management and fracture prevention in postmenopausal women and men over 50 years of age . March 2024 .
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