Diabetes is the leading cause of nontraumatic lower limb amputation. Although the incidence of amputation in patients with diabetes varies widely across different industrialized and nonindustrialized nations, studies estimate the presence of diabetes increases the relative risk of amputation by a factor of 15 to 20.^17,18 This risk also varies across ethnic and socioeconomically diverse groups.¹⁹ A study by Resnick et al²⁰ reported that the 8-year cumulative incidence of lower limb amputation for Native American with diabetes was 4.4% and that increased risk was associated with male sex, renal dysfunction, increased ankle-brachial index, and poor glycemic control.

In 2005, the World Health Organization estimated that with appropriate basic management and care of diabetes, up to 80% of all diabetic foot amputations performed were preventable.²¹ Aggressive, comprehensive diabetes management, in addition to appropriate screening and treatment of PVD, can prevent many cases of lower limb amputation. Although it is generally understood that diabetes increases the risk of amputation, especially with secondary microvascular disease, the opposite relationship is less well known. As with cardiovascular disease, diabetes is more likely to develop in individuals with traumatic amputation as they age.²² Individuals with amputation have higher resting insulin levels compared with healthy control patients, which likely reflects a greater insulin resistance. Moreover,
this appears to be independent of body mass index, blood pressure, and plasma lipid levels.²³

Weight gain after limb loss can have substantial detrimental effects on overall health, mobility, and quality of life. Kurdibaylo²⁴ reported that weight gain is greatest during the first year after amputation; the likelihood of obesity increases with more proximal lower limb amputation (37.9%, transtibial; 48.0%, transfemoral) and with bilateral amputation (64.2%). In addition to the overall health risks associated with obesity, excessive weight gain also can contribute to additional challenges to mobility, proper socket fitting (especially with weight fluctuations), and excessive stress on remaining musculoskeletal structures. Within the first 3 months after amputation, tobacco and alcohol use are prevalent (at 55.7% and 72.0%, respectively); of note, despite a mean bodyweight increase of 23 lb during that time, only tobacco use and alcohol consumption were related to development of secondary overuse musculoskeletal conditions.²⁵ Although individuals with upper limb amputation have been reported to have a higher incidence of overuse injuries to the shoulders, elbows, and wrists,²⁶ those with lower limb amputation and associated obesity are also more likely to sustain upper limb injuries, particularly when relying on their upper limbs for transferring, wheelchair propulsion, or assisted ambulation. Attention to caloric intake, maintaining a healthy diet, and regular exercise should be incorporated into the early treatment of individuals with both upper and lower limb loss.

Although upper and lower limb prostheses improve functionality for patients with amputation, the socket interfaces for these devices have been reported to be problematic, especially when fitting individuals with short residual limbs, or those with substantial weight fluctuations, muscular atrophy, or pressure ulcerations.^27,28,29,30 Unlike the palms and soles, which are specifically equipped for bearing high loads, residual limb skin is considerably thinner, resulting in the high frequency of skin-related complications associated with prosthesis use.³¹ The challenges of socket fitting extend beyond issues of physical comfort and include heat dissipation, excessive sweating,^32,33 skin irritation,^34,35 and, for those with lower limb loss, the inability to walk on challenging terrain.³³ One study investigated skin breakdown in individuals with transfemoral amputation and reported that 30% of patients (26 of 86) had unhealed wounds or damaged skin.³⁶ Dudek et al³⁷ retrospectively examined the charts of 745 patients with 828 lower limb amputations. More than 40% reported at least one skin problem, but the cause of amputation (trauma versus PVD) or the presence of comorbid PVD did not correlate with an increased risk of skin problems. The factors associated with an increased incidence of skin problems were amputation level (four times more common with transtibial than transfemoral amputation), being employed or unemployed compared with the retired study cohort, and using either a single cane or no gait aid. Common skin complications included ulceration, epidermoid cysts, follicular hyperkeratosis, calluses, verrucous hyperplasia, atopic eczema, bacterial folliculitis (caused by Staphylococcus aureus), tinea infection (caused by Trichophyton rubrum), dermatitis, friction erythema, and other rashes.³⁸ Osseointegration, direct skeletal attachment of an external prosthesis, is becoming a more established treatment option for individuals with lower (and upper) limb amputation; substantially improving upon traditional socket-based prostheses, certainly mitigating skin-related complications but also with potential to provide substantial benefits in functional outcomes and overall quality of life.^39,40

Degenerative joint disease and other musculoskeletal overuse injuries also have been reported as a long-term consequence of major limb loss. Even with advances in rehabilitation care and prosthetic technology, individuals with major limb loss report a considerably higher prevalence of musculoskeletal conditions, with associated interference in daily activities and reduction in quality of life.⁴¹ For example, among service members with lower limb amputation, the 1-year incidence of developing at least one overuse condition ranges from 59% to 68%;⁴² the corresponding incidence for those with upper limb amputation ranges from 60% to 65%.⁴³ The risks of these complications tend to differ by etiology (traumatic versus vascular), location (upper versus lower limb), and severity (transfemoral versus transtibial amputation). The risk can be further influenced by the duration of time post-injury, because most active ambulators are exposed to continued abnormal body mechanics associated with long-term prosthesis use. Early recognition of these conditions and a more thorough understanding of the mechanisms that contribute to these problems can help guide both rehabilitation and prevention strategies.

The frequency and severity of low back pain among individuals with lower limb loss have been well documented, with estimated prevalence ranging from 52% to 89% (substantially higher than the general cohort, 12% to 45%).^44,45,46,47 Moreover, a considerable number of individuals with lower limb amputation reported that their back pain was more bothersome than their phantom or residual limb pain and more negatively affected their quality of life.⁴⁸ Low back pain is a multifactorial disorder, emphasizing the need for the application of a comprehensive, biopsychosocial model to better understand its development following amputation.⁴⁹

Physical (biomechanical) risk factors likely play a strong contributing role in low back pain development and/or recurrence among individuals with lower limb loss.⁵⁰ Focus group interviews have indicated that individuals with lower limb loss perceive uneven postures and compensatory movements of the back as major contributing factors to their pain.⁵¹ Biomechanical studies report larger, more asymmetric trunk movements as common gait
features secondary to lower limb loss, including larger forward trunk flexion and sagittal range of motion, as well as lateral trunk flexion (largest in prosthetic stance).^52,53 Repeated exposure to such abnormal trunk motion can predispose individuals with lower limb loss to low back pain through stimulation of embedded nociceptors and/or increasing spinal loads.^54,55,56 With increasing spinal loads, increased and asymmetric trunk postures and motion impose higher demands on trunk tissues to offset the gravitational and inertial demands of the trunk. Trunk muscle responses are particularly important in responding to spinal loads because of their relatively small moment arms in relation to external forces and/or moments.⁵⁷ Among individuals with lower limb loss versus without lower limb loss, measurements of electromyographic activities of the thoracic and lumbar erector spinae identified earlier and more prolonged activations during walking.⁵⁸ Because of the cyclic nature of gait, even small increases in load, particularly resulting from muscle forces, could accelerate degenerative joint changes over time.⁵⁹ In addition, the presence of pain is likely to further influence these responses, resulting in the recurrence and eventual chronicity of low back pain. Specifically, individuals with transfemoral limb loss, with versus without low back pain, tend to walk with more sustained lumbar rotation toward the prosthetic limb, perhaps because of fear of pain with trunk lateral flexion, which was associated with greater pelvic elevation/hip hiking.⁶⁰ Other studies have illustrated either greater axial rotational excursion with low back pain,⁶¹ or oppositional motion patterns in the sagittal and transverse planes.⁶² These individuals also have altered coordination and movement variability between the trunk and the pelvis in the frontal and sagittal planes,⁶³ which are consistent with uninjured individuals with low back pain.