Obesity and Type 2 Diabetes Impacts on Late Life Bone Fragility, Falls, and Fractures: A Narrative Review and Commentary

Is the combination of falls and bone attrition with age of concern in the context of the obese older adult suffering from type 2 diabetes?

Are there indications that more holistic preventive care approaches across the lifespan as well as more study in this realm will prove fruitful?

Sarcopenia, a health condition characterized by an age-related decline in muscle mass and strength, and a replacement of muscle tissue by fat, is being shown to raise the risk of falls, fractures, disability, and mortality in its own right and is frequently exacerbated by the presence of an obesity linked high muscle fat ratio that reduces bone protection and function ⁵. Unsurprisingly, type 2 diabetes when induced by or co-occurring with obesity may well exacerbate an emergent sarcopenic state and its oftentimes multiple adverse health and wellbeing ramifications, thus contributing to the growing clinical challenges of high numbers of aging adults where these conditions when they exist or co exist are associated with an increased risk of injurious falls ⁶. However, this is not a linear uni-directional associations or one readily reversed because weight reduction driven by artificial appetite suppression or lifestyle methods may not induce or reverse a predictable and desirable bone or muscle status in absence of continuous efforts to pursue health eating and/or exercise practices, plus any needed calcium, protein and vitamin D supplementation. Rather, a sole reliance on anti-obesity strategies may potentially compromise muscle health as well as bone health inadvertently and progressively ^{6, 7, 8, 9, 10}.

This abovementioned argument is not just of theoretical interest, but one of immense relevance as societies age because these overlapping conditions are strongly associated with bone fragility ⁶, a strong fracture risk determinant in its own right ^{9, 11}, as well as in cases with type 2 diabetes ¹² and those with clear vitamin D deficiencies ⁷.

Osteosarcopenic obesity , which may stem from as well as further compromise physical function, metabolic health and overall life quality also increases the risk of injurious falls, one or more bone fractures and soft tissue injuries, possible prolonged hospitalizations, cardiometabolic complications and premature mortality ⁵. In women transitioning through menopause, declining estrogen levels that accelerate fat accumulation and muscle loss may be further compromised, while also heightening susceptibility to osteoporosis, hypertension, dyslipidemia, type 2 diabetes and certain cancers that are often worsened in the face of obesity ¹. A parallel vitamin D deficiency may likewise hasten progressive bone deterioration and muscle and adipose dysfunctions, and the osteosarcopenic obese phenotype is strongly correlated with an increasing risk of fragility fractures, injurious falls, functional and metabolic declines, plus higher morbidity and mortality rates ⁷. 

Numerous publications over time that have attested to the key role of bone and bone health as a means of protecting vital body organs, and affording static and dynamic support to the human when upright, plus immune support, as well as serving as strategic sites for muscle tendons, ligaments and capsular attachments continue to show how lesions or deficits in bone significantly reduce the well being of the aged. Indeed, similar to other body organs, bone is a living tissue, but is not one immune or impervious to breakdown as a result of factors other than age. In terms of our examination of the specific theme of bone health and its association with obesity, a topic of increasing interest in this regard, and more so now in the face of the onset of bone fragility and the overall failure of medications and related options to avert this. We specifically elected to ascertain what link exists between obesity and bone health and its possible impact on fracture control in the elderly. Of interest was the validity of the premise that the impact of obesity on bone mineral density deposits is one favoring a bone protective response against sustaining a fracture in the case of a fall, although this is despite the negative influence of this belief and the strong belief in the application of anti-obesity medications or injections that control appetite to afford significant weight losses that thereby restores health including bone health. However, this does not accord with the data wherein bone fragility may well be magnified in the face of co existing type 2 diabetes, an osteoporotic mediator in its own right, and one where the control of glucose via pharmacologic approaches may independently impact bone mass negatively and progressively ¹².

In addition, bone tissue houses important minerals and ions that can be released or stored in a controlled manner to provide constant concentrations in body fluids as required, and this relatively dynamic organ that undergoes significant turnover compared to other organs in the body may yet be affected negatively by multiple factors such as obesity, and its dual association with type 2 diabetes, even when these conditions appear to be effectively controlled or minimized using standard pharmacologic approaches. Indeed, despite an intuitive beliefs to the contrary, obesity and osteoporosis, a disease that is associated with progressive bone loss and fracture risk are not only both common chronic related disabling conditions that appear to be increasing over time rather than decreasing, but can readily occur in tandem, thereby engendering high rates of morbidity and mortality, especially in older adults with an osteoporosis diagnosis.

There is also increasing evidence that the relationship between obesity and bone may not be as protective against fractures as previously believed because not only may bone homeostasis in general be altered in multiple ways by the presence of excess body fat that can impair bone integrity and bone remodeling long before efforts to control weight are implemented but even after that ⁶. It also appears that obese cases who may well be weaker and at risk for falls at higher rates than the non obese ⁶ and obesity in the form of visceral fat in particular, appears to harm bones collectively over time, possibly raising the risk of incurring osteopenia/osteoporosis especially in the older poorly nourished or inactive adult unless apprehended, and countered in a timely effective manner ⁷. 

Thus, even if it is accepted that the presence of any excess body weight can help to build bone, there are several studies that highlight pathways whereby excess weight can yet pose an unanticipated bone fracture or bone damage risk at all ages. This is due in part to a possible obesity associated array of adverse inflammatory impacts on bone genes and bone cell physiology, as well as having diverse negative metabolic influences ⁸, for example in cases with type 2 diabetes who are obese ⁹, as well as a possible ensuing high muscle fat content, weakness, and reduced muscle mass ⁶. 

Piñar-Gutierrez et al. ¹⁰ recount that the recent scientific evidence that has emerged in this regard and that shows an increased risk of fractures among cases deemed to obese and who have an especially high degree of visceral located fat is surely one of ongoing concern because this is increasingly common. One reason for this may be that muscles in that region and others may be that may be infiltrated by excess fat may limit bone protection if a fall occurs as a result of possible deficient muscle reflex and suboptimal impact attenuation responses. Moreover, those who also suffer from obesity associated inflammatory responses and those who use diabetes medications that induce confusion, may foster a state of chronic repetitive joint injuries that may hasten the onset of osteopenia in its own right if sedentary behaviors become more entrenched in response to heightened pain and fears of falling ¹¹.

Indeed, it appears multiple obesogenic-associated metabolic disturbances not only impact bone homeostasis negatively, but can affect bone quality detrimentally over time if the obese person is sedentary or less inclined to move than normal weight similar age individuals. They may thus exhibit various degrees of bone fragility, that progressively impact bone cellular processes as well as various alterations in local bone homeostasis and systemic metabolism ⁷ and metabolic disorders ¹², especially if undetected or only detected when the condition is basically irreversible ¹³.

Hsu et al. ¹⁴ found that the risks of an individual acquiring osteoporosis, osteopenia, or nonspine fractures was significantly higher for subjects with a higher percentage of body fat independent of body weight, physical activity, and age. As such it appeared that having a high fat mass could impose a negative effect on bone mass that is different from that of normal weight-bearing. Other research has revealed that beneficial improvements in bone mineral density do occur in men with diabetes ¹⁵ or overweight status, along with an enhancement in bone strength, but other bone attributes were not examined. On the other hand, Lopez-Gomez et al. ¹⁷ found postmenopausal women who were deemed obese tended to show lower levels of bone formation markers than those deemed to be of a healthy weight. In addition, other data indicate bone quality in the obese case may not be sufficient to successfully avert a fragility fracture because other factors are involved ¹⁶. For example, a role for muscle and possible sensory response changes cannot be discounted, along with a high risk of developing severe co-morbid health conditions that play a role in influencing bone quality ¹⁸. Bone as well as various body systems may also serve as a ‘fat-depot’ that may mediate a range of obesity associated low-grade inflammatory responses that may not only alter the expression of multiple life negating cellular processes, but harmful molecules and chemicals that can adversely affect bone metabolism, and result in its attrition ¹⁹.

Another explanation is that since adipocytes and bone cells known as osteoblasts are derived from the same stem cell source, the presence of obesity may foster more adipocyte differentiation than osteoblast differentiation. These increased numbers of bone adipocytes are found to release a number of pro-inflammatory and immunomodulatory molecules that up-regulate the formation and activation of osteoclasts, a bone cell that removes excess bone, thus favoring bone fragility. As well, the persistent impact of excess body weight, while possibly favoring bone mineral increases, may yet exceed the overall mechanical threshold of the bone, especially in females if other obesity associated health conditions prevail that heighten fracture risk, such as dynapaenic abdominal obesity and/or altered bone blood flow ^{20, 21} despite any favorable body weight increases in bone mineral density ²². Rather, this potentially greater risk of an injurious fall and chances of a bone fracture at one or more bone sites in the obese subject may involve an array of complex metabolic as well as neuromuscular, cognitive, and circulatory factors as well as related biomechanically mediated impacts and their interaction with bone viability as well as vulnerability acquired in the face of certain medications ^{24, 25, 26}, poor diets, and adults exhibiting abdominal obesity ^{4, 20, 27}.

According to Rikkonen et al ²⁸, the presence of obesity is associated with the earlier than expected rate of sustaining a hip fracture injury, a serious debilitating injury associated with a higher than desired post fracture mortality rate and chances of developing complications following a fracture that may yet persist even in the face of successful bariatric surgery ²⁹ or various glucagon uptake inhibitors in those with diabetes ³⁴. Moreover, this cycle may persist even in the face of semaglutide anti obesity interventions factors as a result of the unaffected or altered biomechanical factors associated with a high falls risk ³², as well as possible hormonal factors, and alterations in muscle protective responses, muscle strength capacity and fat ratio that can undermine inherent protective bone impact functions and hasten the emergence of osteoporotic fractures especially in the presence of excess or increasing muscle fat mass in the trunk and arm regions and despite weight reduction efforts ^{30, 32, 34, 35, 38, 41, 45}.

Importantly, if a falls event occurs unexpectedly, the presence of obesity, especially that located in the abdominal area may yet disrupt any prevailing bone morphology via its mechanically induced inflammatory impacts and others ^{33, 34}, and may be especially accentuated regardless of body mass distribution in those categorized as being morbidly obese ^{36, 39}.

As argued by Crivelli et al. ³⁷ when viewed as a whole, it seems fair to conclude both visceral and subcutaneous fat may be detrimental to bone health in pre- and postmenopausal women, as well as men and in both cases severe obesity may increase the risk for incurring a fall and subsequent fracture as well as poor healing trajectories thereafter, even in young adults.

Moreover, in view of what has been observed relative to the fat muscle ratio variable in elderly persons arm and trunk muscles ³⁸, the belief that obesity confers protection against bone fractures must be challenged especially if other conditions affecting people with obesity, such as type 2 diabetes that can foster osteosarcopenia- a debilitating condition characterized by concurrent bone loss and muscle wasting, prevails ³⁹.

Obesity is also associated with a possible vitamin D deficiency ⁷, as well as impaired muscle function, and sarcopenic phenotypes, and possibly thereby with a further fracture risk ⁴¹ and damage to both the bone itself and/or the surrounding soft tissue and its structures. Indeed, contrary to expectations, individuals diagnosed as being obese and having type 2 diabetes do appear to have substantive impaired bone quality alterations and an elevated risk of fragility fractures, despite their higher and/or unchanged bone mineral density ⁴⁹ and often even in the face of efforts to alter bone cell metabolism ³⁴.

Although the effect of obesity on fracture risk appears site-specific with a reduced risk for several fractures (e.g., hip, pelvis, and wrist) and increased risk for others (e.g., shoulder, ankle, upper leg, elbow, vertebrae, and rib), this may be linked to the degree to which body weight/body mass index a risk factor for falling in the elderly ³¹ may prevail due to their higher sway area and sway ranges, plus a lower complexity of anterior-posterior center of pressure responses that may impact dynamic balance adversely ³².

Obese older adults with a type 2 diabetes and who may have a high falls risk may also have a greater risk of upper leg, foot, shoulder, and total fractures occurrences than expected depending on falls location and age, but especially if they have abdominal fat excesses, exhibit dynapenia, subnormal lower limb or gait biomechanics, and/or have painful foot ulcers [40, 47. 50]. 

In this regard, Gkastaris et al. ² conclude the interaction between obesity and bone metabolism even though complex and not fully understood to date must take note of the possible effects of obesity on the multiple skeletal attributes other than bone that might lead to one or more bone fractures for neuromechanical reasons, as well as possible increases in bone marrow fat content ⁴⁰, alongside subcutaneous fat and muscle fat increases, muscle strength, mass and reactivity declines especially in the presence of one or more metabolic diseases such as chronic type 2 diabetes that can impact bone metabolism, bone vascular and energy associated mechanisms, muscle endurance, and cognitions highly adversely ^{41, 45, 54}.

In particular, obesity correlates that are linked to multiple chronic inflammation influences, excessive oxidative stresses, as well as possible impaired glucose control and altered bone metabolism and marrow adiposity, plus dizziness, may especially impair bone quality directly or indirectly regardless of bone mineral density and insightful efforts to offset this adverse and potentially serious reactive cycle appear essential to prevent these mechanisms from unduly undermining bone micro architecture and engendering an unwanted progressive state of bone fragility ^{33, 45}. The role for muscle power and strength declines observed in type 2 obese diabetes sufferers ⁴⁴ as well as the possible persistent obesity associated gait abnormalities should also be dealt with in a more timely manner and prioritized accordingly, not ignored ^{46, 47, 54}.

In addition more attention to controlling triglyceride levels in the context of type 2 diabetes is warranted due to their adverse influence on fat distribution patterns as well as bone mineral density levels and bone volume ⁵¹. The presence of bone inflammation, altered muscle activation, dynapenia, and excess body weight influences on joint loading, plus a type 2 diabetes declining signaling power of the Wnt transduction cell regulation pathway potentially implicated in this regard also warranted future attention ^{45, 47}.

In addition, the allied influence on bone of continuous over nutrition, poor nutrition, fears of falling, and a resultant state of physical inactivity and limited mobility warrants clarification as does the role of obesity associated musculoskeletal health issues, including skeletal muscle atrophy and dysfunction ^{44, 48, 53, 54}. Indeed, it appears that even if mechanical loading has positive effects on bone mineral content, this may not suffice to counter fractures in the obese case who has fallen and where low-grade systemic inflammation is probably present alongside a degraded degree of dynamic stability and muscle reactivity ^{49, 50} and possible presence of extensive frailty ⁶⁶ in those with health conditions such as osteoporosis or others requiring steroid interventions ⁶¹. Moreover, a lab study has revealed aging related obesity may not only impact bone structure adversely, but may suppress vital muscle-nerve communications that thereby contribute to- rather than resolve- type 2 diabetes functional deterioration impacts ⁶². In addition linkages to falls due to dizziness are often present but not duly perceived as injurious ⁶⁷. Obesity in its own right has a negative effect on muscle force generation and slow muscle contractile kinetic responses that could injure bone regardless of its mineral density ⁷¹.

Additionally, chronic diseases such as type 2 diabetes may deplete bone mass inadvertently in its own right while negatively impacting muscle function and joint protection as well as postural control. This interrelated array of health issues, far from being of only modest concern in many cases and not well understood and poorly palliated at present, that is challenging to reverse, surely predicts a costly burgeoning public health concern in all aging societies in the future if weight control interventions as well as falls and osteoporosis prevention attempts are unsuccessful in offsetting late life bone fragility and a host of progressive neural and biodynamic deficits ³⁴.

Despite the obvious limitations of this umbrella overview of obesity and bone as this pertains to older adults with type 2 diabetes and their wellbeing, we conclude:

1. An interactive negative role for obesity in mediating or moderating bone fracture risk, bone density, and bone integrity prevails at all ages and cannot be readily discounted by those who seek to foster healthy aging across the lifespan.

2. Fractures as well as fracture nonunion are increasingly recognized as an outcome of metabolic disorders such as obesity and type 2 diabetes that demand attention, even though the molecular mechanisms underlying impaired fracture risk as well as healing remain incompletely understood ⁶⁰.

It is further concluded that the parallel between diabetes, metabolic disease and bone, and a possible interactive impact of excess weight on bone metabolism, as well as a declining ability to absorb load in a timely well modulated manner plus a potent array of inflammatory factors may explain the paradox of bone fractures in the face of obesity associated increases in bone density and should be studied further.

In addition, efforts across the lifespan are imperative to avert childhood and adult obesity and to address this issue more forcefully and consequentially as regards a life time of suffering for many as well as untold public health costs in the face of inaction and the limitations of pharmacologic or weight loss interventions alone. Indeed, it appears weight loss alone in a previously obese case may exacerbate bone dysfunction and malformation including cortical and trabecular bone losses unexpectedly, rather than alleviating adverse obesity linked bone structural and possible balance and gait associated impacts in those with abdominal obesity or obesity in general ^{65, 70, 72}.

At the same time, unaddressed falls risks and a failure to encourage an active lifestyle can undoubtedly further heighten the risk for exponentially increasing health costs as well as immense human suffering both physical and mental as well as immunological and metabolic that is not necessarily inevitable, but somewhat modifiable ^{5, 69, 73, 74}

While an individualized multidimensional approach to preventing obesity is desirable as far as mitigating serious falls and bone fractures in later life in the context of weight induced type 2 diabetes, and a bone loading mediator in its own right, practitioners cannot be expected to yield favourable outcomes without very careful and comprehensive analyses of the most likely physiological mechanisms underlying bone structural and falls mechanisms in the context of both obese manifestations as well as chronic type 2 diabetes based on isolated thematic non inclusive study approaches and their exaggerated focus on vicarious forms of weight management rather than behaviour changes that may yet underlie a bone fracture risk. Indeed, the persistent impacts of a life of poor nutrition, inactivity, alongside obesity linked disadvantageous cognitions and possible neuromechanical aberrations, in the face of aging and poor obesity management presumably contribute enormously to the public health care burden associated with one or more fractures in later life, especially if ignored or treated too late and without due insight ^{54, 55, 68, 72, 73}.

In particular, the myth that overweight older adults or youth or those with type 2 diabetes are protected against fractures or bone loading alterations, rather than at risk for injury may not only fail to address salient modifiable bone fracture risk factors such as muscle strength losses or those yet uncovered ^{72, 73}, but may allow for more risky rather than protective behaviors or diminished confidence beliefs in the older adults self-generated abilities to protect against both excess bone structural deficits as well as falls ⁵⁵. In addition the imperative to assure adequate calcium and vitamin D exposure/ intake as well as exercise participation, health education, food access, outdoor and indoor safety issues, and concerted efforts to foster weight loss and control glucose levels largely pharmacologically may fail if not encouraged or continuous or duly recognized as salient.

In this regard, He et al. ⁵⁹ imply that rather than an depending on or seeking an isolated pharmacologic solution to weight management, a weight loss-targeted lifestyle intervention may better protect against unwanted bone mineralization and structural alterations as well as falls particularly in the face of an induced rapid weight loss strategy that may yet be harmful to bone and/or fail to return it to its control state if introduced solely as a tertiary rather than as a primary prevention strategy ⁶⁵.

Childhood and adult obesity prevention efforts, rather than late life palliative interventions as well as bone sparing even in diabetic cases appears to offer a more universal chance of saving lives and is in our view increasingly imperative to overcome obesogenic external socially derived highly negative health influences as well as nutrition based bone deficits in our view, and should not neglect the allied importance of health disparities, nutrition access, efforts to discourage sedentary lifestyles, fast foods, excess screen time, advertising of non nutritious foods, and limited vitamin D exposure as this pertains to bone and muscle health as well as cognitive health and sarcopenic obesity-falls linked attributes ^{54, 66}. In particular, the specific role of uncontrolled diabetic osteopathy which is poorly studied and why or how obesity may affect some forms of fracture and not others also warrants possible targeted consideration, as do the methods of establishing obesity and its associated apparent bone based and muscle function ramifications, that may well be somewhat reversible ^{68, 73, 74}.

In addition to the above public health implications noted here we urge the practitioner to also:

· Actively aspire to inspire health decision makers and researchers more effectively as regards the immense need for obesity preventive that embodies a series of proactive options, opportunities, and environmental and sociological possibilities that may allay late life fracture associated disabilities that stem from obesity rather than aging alone.

· Portray a less fatalistic stance that nothing can be done when communicating with an aging client or young at risk person.

· Be willing to form collaborative relationships with governments and health agencies concerned with healthy aging in this regard as well as serving as a resource agent for community members.

· Educate the public as well as youth and administrators about what they can do to save costs and lives by remaining active and controlling their food choices and intake.

· Conduct regular pre clinical screening tests for obesity and osteoporosis risk on asymptomatic citizens likely to be at risk for falls, motor as well as cognitive dysfunction, and type 2 diabetes including non biological social factors, behavioral, situational, gait mechanics, and environmental predisposing factors.