Postmenopausal osteoporosis is a systemic skeletal disease of
fragility fractures due to the loss of the mass and the deterioration of
the microarchitecture of bone. This study aimed to assess the effects
of raloxifene hydrochloride nanosuspensions (RLX-NSps) on ovariectomized
(OVX)-induced osteoporotic rats, and the underlying mechanisms were
also investigated in vivo and ex vivo. RLX-NSps were successfully
prepared, and the obtained RLX-NSps had a mean particle size of (91.17 ±
0.73) nm, PDI value of 0.201 ± 0.03 and zeta potential of (36.3 ± 1.8)
mV. RLX-NSps showed a clear colloidal solution with light yellow
opalescence. RLX-NSps were stable in artificial intestinal fluid,
artificial gastric fluid, PBS, isotonic glucose and physiological
saline.Raloxifene powder
The OVX mice were administered an RLX-NSps or RLX solution for 3 weeks.
The bone micro-tomographic histomorphometry and bone mineral density
(BMD) were assessed by micro-CT, and the biochemical markers procollagen
type I N-terminal propeptide (P1NP) and beta-isomerized C-telopeptide
(β-CTX) were determined from serum. Finally, primary bone marrow stromal
cells (BMSCs) were isolated from the tibia and cultured to evaluate
cell proliferation and osteogenic differentiation. The results
demonstrated that the RLX-NSp group had a better effect on the bone
microarchitecture than the RLX solution group. Therefore, RLX-NSps could
partially attenuate bone loss more effectively than RLX solution in OVX
mice by inhibiting bone resorption and improving the ability of BMSCs
to proliferate and their osteogenic differentiation to some extent.
Based on these results, nanosuspensions (NSps) may be a promising
delivery system for postmenopausal osteoporosis therapy.
Postmenopausal osteoporosis is a relatively common metabolic bone
disease that leads to increasing skeletal fragility and the risk of
fractures due to rapid bone loss.1–3 Over half of adults over the age of
50 are diagnosed with osteoporosis, and among them, most women have
postmenopausal osteoporosis.4,5 They can be affected with osteoporotic
fractures throughout their remaining lifetime.6
There are two major
therapeutic approaches for osteoporosis. One is anabolic agents that
function by means of improving bone formation, such as parathyroid
hormone,7 and the other is antiresorptive agents, which function by
means of inhibiting osteoclast-mediated bone resorption, such as
bisphosphonates.8 Estrogen deficiency, which is related to the loss of
ovarian function, leads to bone loss and is a marker of osteoporosis as a
result of excessive bone resorption.9–11 To prevent postmenopausal bone
loss, estrogen replacement therapy (ERT) and hormone replacement
therapy (HRT) have been applied.12 It was reported that it can increase
the risk of endometrial cancer and is slightly related to an increased
risk of breast cancer after using estrogen for a long time.13,14 In
contrast with estrogen, many studies have demonstrated that RLX has no
side effects in terms of the stimulatory effect on the endometrium and
the breast.15–17
