Afrikaner 'giants' may hold key to osteoporosis

A small group of Afrikaners who have bones "as solid and heavy as rocks", according to a surgeon, could hold the key to curing osteoporosis.

The patients have an uncommon genetic mutation that causes the excessive and rapid formation of dense bones (sclerosteosis). The condition has triggered the development of a drug to improve bone density.

"This could be the cure for osteoporosis," said ear, nose and throat surgeon Dr Louis Hofmeyr, who specialises in operating on these patients.

Osteoporosis is almost the opposite of sclerosteosis: it is a progressive bone disease that can lead to an increased risk of fractures.

Professor Stephen Hough, president of the National Osteoporosis Foundation of South Africa, said of sclerosteosis sufferers: "They have immense skulls and prominent jaws and can be as tall as giants. The SOST gene means the normal control and inhibition of bone growth goes out of the back door."

Only a handful of patients globally, mostly in Holland from where Afrikaners trace their ancestry, also have a variety of "marble bone disease".

Across South Africa, 75 people have been diagnosed with sclerosteosis and about half of them are still alive. Sufferers usually die in their teens if the symptoms are not picked up early enough.

Theuns Botha of George in the Western Cape said his son, who is now nine, had two attacks of facial paralysis and was wrongly diagnosed as a toddler.

When they consulted ear, nose and throat specialist Professor Herman Hamersma, who is retired from the University of Pretoria, he immediately identified sclerosteosis.

"Any child in South Africa with facial paralysis needs an X-ray to establish it is not marble bone disease," said Hamersma.

Deformed fingers and toes at birth, acute facial paralysis and loss of hearing are signs of the condition. Every paralysis damages the facial nerves and, without surgery to grind away bone, the face can become an almost frozen mask.

Hofmeyr, who is also from Tuks, said: "This is a recessive gene that can skip a generation and the diagnosis is often missed. The brain function is normal, but the bones are abnormal.

"Patients can die from compression of the brain, usually in their teens. If they are over 25 or 30, they are likely to survive long term."

A 44-year-old patient from Cape Town, who preferred not to be named, said: "I was born with my fingers joined. I had surgery when I was about five years old to remove bone, and I have not had a day's trouble since. Early diagnosis gives you every chance for a normal life.

"I wouldn't consider myself the handsomest guy, but I've been happily married for 19 years and have two healthy teenagers. Of course, I played rugby - lock - and I did some serious damage to myself, but never broke a bone," said the man, who is 2.09m tall.

Botha said his son was well adjusted and intelligent despite having had "six major operations to his head".

He is lobbying to have research into the prevention of uncontrolled bone growth put on the agenda.

"These are huge ethical issues not unique to people with sclerosteosis. Industry can fund research against osteoporosis and make so much money out of a small group of people, but nobody is willing to support research on this orphan disease."

Afrikaners with the SOST gene lack sclerostin to inhibit bone growth. Botha has a theory that injecting sclerostin into SOST-bred mice will alter their bone metabolism and is determined to test it.

"Diabetes patients inject insulin, so I thought why not replace the sclerostin?"

Botha, a visiting researcher at Tuks and the Onderstepoort veterinary school, said: "I just need four to six SOST-mice [bred to delete the sclerostin gene] and sclerostin to prove this principle, but it is expensive."

Hamersma thought the idea was "wonderful".

Hamersma and Professor Peter Beighton, who was head of the human genetics department at the University of Cape Town, worked together for decades to unravel the mystery of these Afrikaners' bone metabolism.

US collaborators at the Darwin molecular biology laboratory in Seattle had the technology to isolate the SOST gene for them in 1996.

"They paid all the expenses for [Dr] Jessica Gardner to go over with the blood of 15 of our patients in her suitcase," said Hamersma. Beighton added: "The ultimate aim was to find an effective treatment that benefits patients."

Botha lives with a "fire in his belly" to find a cure for his son. "When he is 21, I want to be able to tell him ... I did everything I could for him."