Intervertebral disc degeneration in a naturally occurring primate model: Radiographic and biomechanical evidence

Abstract

Classic degenerative disc disease is a serious health problem worldwide, whose etiological basis-mechanical stimulus, biochemical changes, or natural aging-is poorly understood. Animal models are critical to the study of degenerative disc disease initiation and progression and for attempts to regulate, ameliorate, or eliminate it. The macaque represents a primate model with natural disc degeneration that might serve to advance the field; we aimed to provide radiographic (morphologic) and biomechanical evidence of natural disc degeneration in this model. A factorial study design was used to examine the relationship between the radiographic appearance of disc degeneration and its biomechanical consequences. Eighteen macaques of advanced age (22.3 AE 0.9 years) had radiographs taken to assess the degree of thoracolumbar intervertebral disc degeneration using a standard atlas method. Each spine was harvested and dynamic biomechanical tests were performed. Advancing disc degeneration (degree of disc space narrowing and osteophytosis) was associated with increased stiffness, decreased energy absorption, and increased natural frequency of the intervertebral disc. These associations linking the dynamics of the intervertebral disc and its degree of degeneration are similar to those found in humans. Our results indicate the macaque model with morphologic and biomechanical efficacy could aid in understanding the progression of disc degeneration and in developing therapeutic strategies to prevent or inhibit its course. Keywords: intervertebral disc; disc degeneration; Macaca fascicularis; disc dynamics; biomechanics Lumbar intervertebral discs change morphologically, biochemically, and biomechanically with advancing age, 1-10 changes that are characterized as disc degeneration and are implicated as the origin of low back pain. Unfortunately, the initiating and perpetuating factors of disc degeneration are unknown, so despite the pain, disability, and economic loss associated with disc degeneration, intervention and mitigation strategies cannot effectively proceed. Morphologically, dehydration and diminished cellularity of the nucleus pulposus and disorganization and lesions of the annulus fibrosus demarcate disc degeneration. These changes manifest as decreased disc height, increased radial bulging, and osteophyte formation. 11,12 Morphologic changes are intrinsically tied to the biochemistry and biomechanics of the system, and visible and radiographic changes are used to define gradations of disc degeneration. [13][14][15][16] The altered biomechanical response of degenerate disc tissues have been measured. [2][3][4][17][18][19][20][21][22][23][24] Disc stiffness decreases with low-grade degeneration and increases with the most severe degeneration, while energy absorption decreases throughout degeneration. Further, spinal segment range of motion and neutral zone increase with advancing degeneration up to the most severely degenerated discs, where these properties reverse course with increasing stiffness. Unfortun...

Vertebral Bodies or Discs: Which Contributes More to Human-like Lumbar Lordosis?

“…As the morphologic features of the spines of both species are wellcharacterized and we observed no differences between the species, we combined the values for all analyses. Macaques have been used as models of the human condition to study osteoporosis [10,11], osteoarthritis [14,31], and intervertebral disc mechanics [40]. Despite their use as models of human spinal biology, macaques are quadrupeds with little or no lumbar lordosis [1,43].…”

Etiology of lumbar lordosis and its pathophysiology: a review of the evolution of lumbar lordosis, and the mechanics and biology of lumbar degeneration

“…However, degenerative changes occur with similar frequency in spines of primates in captive populations despite their lack of lumbar lordosis. 140 In contrast, wild populations of old world primates show a remarkable absence of degeneration. 95 The challenge of accurately aging wild primates makes it difficult to determine if degenerative spinal conditions in captive populations are a result of longer life spans in captivity or forced changes in lifestyle.…”

“…Interestingly, captive populations of macaques are reported to spend a significant portion of their waking time sitting, unlike their wild counterparts. 140 The occurrence of degenerative conditions in human spines motivates the question of whether humans are now outliving their evolved form. Over 3 million years ago the maximal lifespan of our human ancestors was similar to that of great apes, approximately 50 years.…”

Comparison of vertebral and intervertebral disc lesions in aging humans and rhesus monkeys

“…We compared the rhesus monkey thoracolumbar transitional zone to the human lumbar region, because these are the areas that have been previously described as the region of peak spinal OA in the spines of the two species 27, 28 (demonstrated in Figure 1). Futures studies should investigate degeneration patterns in the mid to lower lumbar rhesus monkey spine, as there is a slight lordotic curve that may render degeneration trends similar to human lumbar discs.…”

“…Naturally-occurring spinal OA and similarities in disc degeneration biomechanical properties 27 and pathological patterns makes rhesus monkeys an excellent model of age-related spinal OA and disc degeneration in humans. The average life span of captive rhesus monkeys is 27 years and they age at a rate roughly three times that of humans 13,29,30 .…”