Clinical Pearls:
- Currently, no osteoanabolic
treatment exists for osteoporosis, other than parathyroid hormone.
- Romosozumab is the first
humanized, osteoanabolic, anti-sclerostin monoclonal antibody which binds
and inhibits sclerostin leading to increases in bone formation and
decrease in bone reabsorption.
- This regimen is a new approach
in treating osteoporosis whereby patients received sequential anabolic
therapy with two biologic agents-Romosozumab and Denosumab.
- One year of treatment with Romosozumab resulted in clinically significant lower risk of vertebral and clinical fractures in postmenopausal women and resulted in substantial gains in Bone Mineral Density (BMD) at the spine and hip.
According to
the statistics by International Osteoporosis Foundation (IOF) [1]It
is estimated that osteoporosis affects 200 million women worldwide, affecting
one tenth of women over the age of 60, one fifth over the age of 70, two-fifth
over the age of 80 and nearly two-third over the age of 90.[2]
Nearly 1 in 3 women over the age of 50 will suffer osteoporotic fractures
during her life time. Fewer than 25% of patients suffering osteoporotic
fractures receive treatment after the incidence and even among those who start
the treatment, majority of the patients terminate it prematurely.
Currently,
other than the parathyroid hormone analogs all treatments aimed at osteoporosis
are antiresorptive. Researchers have spent resources on
development of anabolic therapies, which led them to novel therapeutic approach
in the treatment of osteoporosis - sclerostin inhibition. Sclerostin is secreted
by osteocytes and acts by inhibiting Wnt signaling, thereby preventing
osteoblast development and function.
Romosozumab
is the first humanized, osteoanabolic, anti-sclerostin monoclonal antibody
which binds and inhibits sclerostin leading to
increases in bone formation and decrease in bone reabsorption.[3]
The Fracture Study in Postmenopausal Women with Osteoporosis (FRAME) is an
international, randomized, double-blind, placebo-controlled, parallel-group
phase 3 trial. The landmark study aims to evaluate the effect of 1 year of Romosozumab (at a dose of 210 mg,
administered subcutaneously monthly) on development of fractures in
post-menopausal women with osteoporosis. The FRAME trial recruited 7180 postmenopausal
women between 55 -90 years of age and they were randomized to receive
either 210 mg of Romosozumab placebo once a month for 12 months.
The study findings
were presented at the at the American Society for Bone and Mineral
Research (ASBMR) 2016 Annual Meeting.[4]
The results were also published simultaneously in The New England
Journal of Medicine.[5]
After I year
of therapy with the monoclonal antibody treatment, patient received 2 doses of
denosumab 60 mg subcutaneously at an interval of 6months. This regimen is a new
approach in treating osteoporosis whereby patients received sequential anabolic
therapy with two biologic agents.
The results were statistically significant since the relative risk of new vertebral fractures was reduced by 75% and the relative risk of a clinical fracture by 36% through 12 months compared to those receiving placebo.
The study
met the coprimary end points of reducing the cumulative incidence of new
vertebral fractures at the end of 1 year and 24 months. By reducing the incidence
of clinical fractures (vertebral and non-vertebral) at the end of 12 months’
secondary end point werealso met, however when only incidence of non-vertebral fractures
was analyzed, the study was short of meeting the goal.
In the study
Romosozumab did reduce non-vertebral fractures but the data was not
statistically significant. This was explained due to the geographical location
of the study population. Majority of the study subjects were from Latin America
were the incidence of non-vertebral fracture is extremely low. When the
analysis was conducted after excluding the Latin American cohort, Romosozumab led
to a significant 42% reduction in the risk of nonvertebral fractures over 1
year compared with placebo patients.
The clinical
benefits seen in trials were also supported by lab results of increase in bone-formation
marker P1NP and decrease in bone-resorption marker β-CTX during the 12 months’
period of therapy.
Adverse
events were reported in control as well as placebo groups equally. Hypersensitivity
reactions were more common in the Romosozumab group along with single incidence
of jaw bone necrosis and atypical femoral fracture.
In an
accompanying editorial, Dr Rosen and Dr Ingelfinger quote "The long-term
treatment of osteoporosis remains challenging, and Romosozumab may be one
answer. More trials are needed before we can embrace a new approach."
The study received
funding from Amgen and UCB Pharma as
well as Dr Cosman received personal fees from Amgen and other pharma company.
The editorial authors are employee of NEJM.
Osteoporosis is a silent process of losing minerals from your bones. They become brittle and fracture easily.There is no pain unless you experience a fracture which is why it is important to look after your bone health with preventive measures.
ReplyDeletehttp://www.bluesupplement.com/womens-multivitamin/