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34 Veterinary Laser Therapy in Small Animal Practice
cells derived from bone marrow and adipose tissue measured how LT can modify the expression of osteo-
were stimulated by irradiation and implanted into the genic genes during bone healing of tibial defects. Laser
experimentally infarcted rat heart, a 50% decrease in was applied every other day and induced upregulation
cardiac infarct size was achieved. [153] Laser increased of bone morphogenic proteins and ALP; histologically,
survival of those stem cells, and the result was increased treated individuals showed enhanced new bone for-
angiogenesis and reduced fibrosis. These experimental mation. [157] Pulse frequency is important, and low fre-
findings have started to have some clinical application: quency has consistently been reported to work better to
a clinical study in 58 patients (20 of whom made up the enhance new bone formation. [158–161]
control group) showed that transthoracic LT decreased Some conditions make it more difficult for patients
cardiac cellular damage and improved cardiac tissue to form new bone, and LT has also been investigated in
healing markers following coronary artery bypass graft- models of bisphosphonate treatment and osteoporosis.
ing operations for coronary vessel occlusion. [154] Bisphosphonates are used in humans for the treatment
The effect of LT on the third type of muscle tissue, of bone metastasis and other skeletal conditions. They
smooth muscle, has also been tested: it stimulates have resorptive and anti-angiogenic effects in the bone,
smooth muscle cell proliferation and metabolism, [155] and because of this some patients suffer a complication
which is relevant to arterial diseases, among others, called bisphosphonate-related osteonecrosis of the
including aneurysm, where there is depletion of jaws (BRONJ). In vitro models show different cell lines
smooth muscle cells. This was later also proven in a rat (including osteoblasts), proliferate more under laser
model [75] : LT significantly decreases abdominal aortic treatment, even when they are incubated with bisphos-
aneurysm progression. phonates. [162] Primary osteoporosis is most commonly
seen in elderly humans, but similar changes can be seen
5.4 Bone healing in small animals due to lack of use, poor nutrition, and
endocrine and renal imbalances. Models of osteoporo-
The first phases of bone healing after a fracture are sis due to estrogen deprivation in ovariectomized rats
quite similar to what happens in other tissues; there is show LT can enhance new bone formation, with and
hematoma formation and an inflammatory phase, with without metal implants. [163, 164]
release of cytokines. Common growth factors such as
VEGF or PDGF, which as you know can be enhanced 5.5 Nerve healing and function
by LT, start playing their roles, but also a set of par-
ticular proteins called bone morphogenic proteins. Animal models show peripheral nerves regenerate
New blood vessels are created, and a few days after the faster after transection and anastomosis when the
fracture there is already an unstable net of early woven animal receives LT. [165, 166] Laser also enhances auto-
bone. Fracture repair usually involves a combination of graft repair of peripheral nerves, and in models of nerve
intramembranous and endochondral ossification, with crushing injury, LT improves regeneration and acceler-
progenitor cells differentiating into chondroblasts and ates functional recovery. [167–169]
osteoblasts. The fibrocartilaginous callus is gradually In spinal cord injury models, the length of axonal
(over a period of weeks) replaced by a more organ- regrowth can double in animals treated with laser,
ized, calcified, and stable callus. This callus undergoes and those animals also achieve a better functional
remodeling in the next few months, following stress recovery. [170] The experimental effects of chronic nerve
forces, until its structure is similar to regular bone. and ganglion compression can be alleviated with LT,
LT enhances osteogenesis: in vitro and in vivo which increases levels of nerve growth factor, acceler-
studies report it increases osteoblast multiplication and ates functional recovery, and decreases the associated
survival, as well as osteoblast metabolism. It induces inflammation. [39, 89] Even in hemisection at T9, LT
alkaline phosphatase (ALP) activity and also osteopon- applied transcutaneously to adult rats increased axonal
tin, a protein involved in the attachment of osteoclasts number and distance of regrowth and significantly sup-
to the mineralized bone matrix, among others. [156] pressed immune cell activation and cytokine/chemok-
The clinical consequence is improved calcification ine expression. [171] For this study, they were using 0.53
2
and fracture recovery. For instance, an experimental W/cm and about 450 J concentrated over a point at
study in rats using polymerase chain reaction (PCR) the hemisection site, irradiating for about 50 min/day
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