Histomorphometric changes following treatment for osteoporosis
C. A. Moreira1 · D. W. Dempster2,3
Received: 23 February 2017 / Accepted: 22 March 2017
© Italian Society of Endocrinology (SIE) 2017
demonstrated that mineral apposition rate (MAR) was
unchanged, confirming that there is no inhibition of bone
mineralization, despite the reduction in bone remodeling
rate. Furthermore, alendronate had minimal effect on the
parameters related to bone resorption such as osteoclast
number and eroded surface. Bone microarchitecture, cancellous
bone volume, and cortical thickness are preserved
with antiresorptive treatments. After 3 years of treatment
with risedronate, a paired biopsy study in postmenopausal
women showed a decrease in bone remodeling associated
with preservation of bone structure. The diminution of
bone remodeling with risedronate is less than that which
occurs with zoledronic acid and denosumab, which are
considered to be more potent antiresorptive agents.
In the FREEDOM trial of denosumab bone, biopsies
were performed after 24 or 36 months of treatment [3].
They showed a significant reduction in eroded surface and
osteoclast number with denosumab compared to placebo.
In addition, dynamic parameters were reduced by denosumab
treatment with the median bone formation rate being
reduced by 97% in comparison to placebo. In fact, double
tetracycline labeling in trabecular bone was observed in
only 40% of the patients treated with denosumab, while
it was present in 100% of the placebo group. However, it
is important to note that, among patients on denosumab,
those who had tetracycline labels and those without labels
had similar circulating bone turnover marker levels. This
finding suggests that lack of labels at the iliac crest does not
necessarily mean absence of bone remodeling in other skeletal
sites [3]. The STAND trial compared denosumab to
alendronate and showed that indices of bone turnover were
lower in patients treated with denosumab than with alendronate,
confirming the more potent antiresorptive effect
of denosumab seen with biochemical markers [3]. Furthermore,
it is important to note that the effects of denosumab
A significant body of information is available regarding
the effects of osteoporosis drugs on bone histomorphometry
[1, 2]. This is, in part, because regulatory agencies
require biopsies to be performed to assess the safety and
mechanism of action of new therapeutic agents. There are
two classes of osteoporosis drugs: antiresorptive and anabolic.
As revealed by bone histomorphometry, each class
has a fundamentally different mechanism of action. Antiresorptive
therapies, such as estrogen, calcitonin, raloxifene,
bisphosphonates, and denosumab, decrease bone turnover,
lowering both resorption, and formation [2]. There are several
histomorphometric studies on the effect of hormone
therapy (HT) in postmenopausal women, providing convincing
evidence of its beneficial skeletal action in preserving
bone volume and structure by decreasing bone turnover.
The reduction in bone remodeling parameters after
treatment with HT is more pronounced than that observed
with raloxifene or calcitonin. Similarly, bone biopsy studies
following treatment with bisphosphonates show a reduction
in the rate of bone remodeling with a decrease in osteoid
surface and in the tetracycline-based, dynamic parameters
of bone turnover: mineralizing surface, bone formation
rate and activation frequency. However, a study analyzing
biopsies obtained after 2–3 years of alendronate treatment
Inscrever-se
0 Comentários