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\begin{document}

\title{Backstory of:~ A randomized, double-blind phase 2 clinical trial of
blosozumab, a sclerostin antibody, in postmenopausal women with low bone
mineral density}



\author[1]{Backstories}%
\author[2]{Robert Recker}%
\affil[1]{Backstories}%
\affil[2]{Creighton University}%


\vspace{-1em}



  
  \date{May 24, 2024}


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This is the backstory of:~\emph{~A randomized, double-blind phase 2
clinical trial of blosozumab, a sclerostin antibody, in postmenopausal
women with low bone mineral density~\cite{Recker_2015}}

Lilly conducted a clinical trial of Blosozumab, and before it was
approved by the FDA, they abandoned it completely.

I suspect that it had to do with adverse events that appeared during the
trial, but I was never a part of the work, and therefore, did not know
anything about why they abandoned it. My work on LRP5, Sclerostin and
WNT signaling ended when my group published the original G171V mutation
in LRP5 as the cause of high bone mass in the family who had the
mutation \cite{Little_2002}.~Sclerostin is a physiologic inhibitor of
LRP5 and WNT signaling in bone, thus a human sclerostin antibody was
thought to be a candidate for development of a bone anabolic agent (by
inhibiting the inhibitor). Amgen is developing Rosozumab, another
antisclerostin antibody. I have not had anything to do with that work,
either.~I am awaiting the outcome of the Amgen presentation to the FDA.
With regard to the story behind our work; how that impactful work came
together, and what were the challenges we faced with the research, the
publication process and/or funding. Most of the work we did was
volunteer work, with no outside funding. The work started in my lab when
a local orthopedist referred a patient to my clinic who was 18 years
old, and had been under treatment 2 years for back pain due to a soft
tissue injury from an auto accident. He reported that her X-rays
``looked funny''. Actually, they indicated she had dense bones. Her DXA
showed T-scores of +6.0. Her mother accompanied her, and at age 52, she
had T-scores of +6.0. A few days later, her father and younger brother
were brought to the clinic, and demonstrated T-scores of
\textgreater{}+0.5, entirely normal \cite{Johnson_1997}.

The work required included traveling all over the U.S. to locate 250
members of the kindred. We obtained blood specimens and densitometry
from 39 of them, and we collaborated with a genomics company to locate
and identify the mutation. We applied for NIH funds, but we were not
awarded funds to do the work, because the reviewers felt that we were
unable to accomplish the work, and even if we did, it was not worth
doing. I remain hopeful that further studies will ultimately show that a
human sclerostin antibody~will lead to a ``cure'' of osteoporosis.

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