Showing papers in "Clinical Reviews in Bone and Mineral Metabolism in 2014"
TL;DR: It is proposed that these two models of interaction are complementary and intertwined providing for a new frontier for the investigation of how bone–muscle cross talk could be fully explored for the targeting of new therapies for musculoskeletal diseases.
Abstract: The complexity of cell interactions with their microenvironment and their ability to communicate at the autocrine, paracrine, and endocrine levels has gradually but significantly evolved in the last three decades. The musculoskeletal system has been historically recognized to be governed by a relationship of proximity and function, chiefly dictated by mechanical forces and the work of gravity itself. In this review article, we first provide a historical overview of the biomechanical theory of bone–muscle interactions. Next, we expand to detail the significant evolution in our understanding of the function of bones and muscles as secretory organs. Then, we review and discuss new evidence in support of a biochemical interaction between these two tissues. We then propose that these two models of interaction are complementary and intertwined providing for a new frontier for the investigation of how bone–muscle cross talk could be fully explored for the targeting of new therapies for musculoskeletal diseases, particularly the twin conditions of aging, osteoporosis and sarcopenia. In the last section, we explore the bone–muscle cross talk in the context of their interactions with other tissues and the global impact of these multi-tissue interactions on chronic diseases.
68 citations
TL;DR: By describing a set of biological, clinical and functional characteristics that are associated with sarco-osteoporosis, this information could be used to inform the design of future trials and to develop interventions for this particular syndrome.
Abstract: Muscle and bone are in constant interaction. With aging, there is a progressive decline in muscle mass, known as sarcopenia, as well as in bone mass, which is known as osteopenia/osteoporosis. Sarcopenia and osteoporosis increase the risk of suffering falls and fractures, respectively. In fact, the simultaneous occurrence of osteoporosis and sarcopenia has been observed in a subset of frailer individuals at higher risk of disability, falls and fractures. However, the particular clinical outcomes that are unique to the sarco-osteoporotic patients remain unknown. In this review, we propose a common mechanism of sarco-osteoporosis and summarize those clinical and biochemical features that are prevalent in sarco-osteoporotic subjects. We expect that by describing a set of biological, clinical and functional characteristics that are associated with sarco-osteoporosis, this information could be used to inform the design of future trials and to develop interventions for this particular syndrome.
29 citations
TL;DR: Exercise is likely to be an effective tool in maintaining bone strength but current interventions are far from optimal, particularly in interventions in early pubertal children.
Abstract: Mechanical stimuli influence bone strength, with internal muscular forces thought to be the greatest stressors of bone. Consequently, the effects of exercise in improving and maintaining bone strength have been explored in a number of interventional studies. These studies demonstrate a positive effect of high-impact activities (i.e. where large muscle forces are produced) on bone strength, with benefits being most pronounced in interventions in early pubertal children. However, current studies have not investigated the forces acting on bones and subsequent deformation, preventing the development of optimised and targeted exercise interventions. Similarly, the effects of number and frequency of exercise repetitions and training sessions on bone accrual are unexplored. There are conflicting results as to gender effects on bone response to exercise, and the effects of age and starting age on the osteogenic effects of exercise are not well known. It also appears that exercise interventions are most effective in physically inactive people or counteracting conditions of disuse such as bed rest. Bone strength is only one component of fracture risk, and it may be that exercise resulting in improvements in, e.g., muscle force/power and/or balance is more effective than those whose effects are solely osteogenic. In summary, exercise is likely to be an effective tool in maintaining bone strength but current interventions are far from optimal.
27 citations
TL;DR: The present understanding about PTHrP’s role to control mineral and bone metabolism during pregnancy, lactation, and fetal development is reviewed.
Abstract: Parathyroid hormone-related protein (PTHrP) was originally identified as the cause of humoral hypercalcemia of malignancy (HHM), a condition that resembles primary hyperparathyroidism and the effects of excess parathyroid hormone (PTH). But HHM is an unusual situation because PTHrP is normally undetectable in the circulation of the child or adult. Instead, most of PTHrP’s actions are now understood to be paracrine or autocrine, and not humoral. However, PTHrP is present in the circulation at measurable levels during fetal development, pregnancy, and lactation. During these time periods, PTHrP has humoral actions that regulate mineral and bone homeostasis independently of PTH. In fact, the existence of PTHrP was also predicted by the characteristic pattern of serum chemistries and PTH in cord blood of normal newborns, and by the normalization of calcium metabolism that temporarily occurs in hypoparathyroid women who breast-feed. This article reviews our present understanding about PTHrP’s role to control mineral and bone metabolism during pregnancy, lactation, and fetal development. Excess PTHrP can also be produced by the placenta or the breasts during pregnancy, or by the breasts during lactation, and in both situations it can lead to hypercalcemia and other clinical features that are indistinguishable from HHM. The highest concentrations of PTHrP are found in milk, and recent evidence indicates that milk-based PTHrP may reduce mineral accretion by the newborn skeleton, but whether it does this through local actions in the neonatal gut or after absorption into the neonatal circulation is unknown.
15 citations
TL;DR: The evidence surrounding potential factors affecting bone health in bariatric patients such as rapid weight loss per se, nutritional deficiencies, effects of fat-derived adipokines and gut-derived appetite-regulatory hormones are reviewed.
Abstract: Despite significant improvement in weight and comorbid conditions, there is growing evidence that bariatric surgery may exert a negative effect on the skeleton. This review has focused on the impact of bariatric surgery on bone health, with the concern that bariatric surgery may increase skeletal fragility and fracture risk by accelerating bone loss. We have highlighted studies evaluating changes in bone metabolism after three commonly performed bariatric procedures including laparoscopic adjustable gastric banding, Roux-en-Y gastric bypass surgery and increasingly popular sleeve gastrectomy. This review has also discussed some of the technical issues faced in measuring bone in obese populations and during dynamic weight loss. There is limited evidence regarding potential mechanisms for the reported observations of increased bone turnover and/or bone loss after bariatric surgery. We have reviewed the evidence surrounding potential factors affecting bone health in bariatric patients such as rapid weight loss per se, nutritional deficiencies, effects of fat-derived adipokines and gut-derived appetite-regulatory hormones. Future prospective long-term cohort studies are needed to define how to quantify bone loss in individuals with obesity, particularly following massive weight loss, and for how long the bone changes continue. These studies will help clarify any negative clinical consequences of these changes, including future fracture risk in this unique group of patients.
12 citations
TL;DR: Computer simulations have demonstrated that local remodeling regulated by mechanosensitive osteocytes indeed produces load-aligned trabeculae and osteons, and may provide a mechanism for damage removal because osteocyte death near the path of the BMU redirects its course to resorb this region.
Abstract: Bone is adapted to mechanical loading. The trabeculae in cancellous bone and the osteons in cortical bone are aligned to the mechanical loading direction. Our bones are constantly remodeled by bone-resorbing osteoclasts and bone-forming osteoblasts, cooperating in so-called basic multicellular units or BMUs. In cortical bone, osteoclasts dig tunnels through solid bone, while in cancellous bone, they dig trenches across the trabecular surface. Osteoblasts fill these tunnels and trenches, creating osteons and hemi-osteons, respectively. How mechanical forces guide these cells is still uncertain, but mechanosensitive osteocytes are believed to orchestrate bone remodeling by sending signals to the cells at the bone surface. Computer simulations have demonstrated that local remodeling regulated by mechanosensitive osteocytes indeed produces load-aligned trabeculae and osteons. The strains around a BMU resorption cavity are concentrated at the lateral sides, away from the loading axis. Strain-induced osteocyte signals from these regions likely repel osteoclasts, forcing them to resorb bone in the loading direction, and at the same time, such signals could recruit osteoblasts to start bone formation. Thus, mechanosensitive osteocytes likely regulate the steering of and coupling within BMUs. A region of osteocyte death (therefore, lacking osteoclast-repelling signals) near the path of the BMU redirects its course to resorb this region. This may provide a mechanism for damage removal, because osteocyte death is associated with microdamage. BMUs may also function with disuse-induced osteocyte signals that recruit osteoclasts to the relatively unloaded region in front of the BMU and inhibit osteoblastic bone formation by osteoblast-inhibiting signals such as sclerostin when the tunnel or trench is sufficiently filled.
11 citations
TL;DR: An overview of a range of biological factors possibly involved in the biochemical cross talk between bone and muscle and the plausibility that such interactions are involved in non-pathological adaptation of both tissues, either in paracrine or in endocrine fashion is discussed.
Abstract: In elderly with a sedentary lifestyle, often suffering from sarcopenia to osteopenia, a training intervention could be an effective countermeasure for bone as well as muscle. Both bone and muscle adapt their mass and strength in response to mechanical loading in part via similar signaling pathways. Bone as well as muscle produces a wide variety of growth factors and cytokines in response to mechanical loading, which are important for their adaptations. It has been hypothesized that in addition to mechanical stimuli, muscle and bone communicate by these factors. Whether such biochemical interaction between both tissues is physiological is a still subject of debate. Here, we provide an overview of a range of biological factors possibly involved in the biochemical cross talk between bone and muscle. In addition, we discuss the plausibility that such interactions are involved in non-pathological adaptation of both tissues, either in paracrine or in endocrine fashion. As yet, convincing experimental evidence for biochemical cross talk between muscle and bone is very limited. Several studies have shown that muscle-derived factors are involved in bone fracture healing as well as in bone adaptation in case of muscle pathology. For involvement of cross talk between muscle and bone in physiological adaptation, there is no definite proof yet. Detailed knowledge of the biochemical interactions between muscle and bone is of clinical importance. It can help to discover pharmacological treatment to be used alone or in parallel with exercise training, thereby reducing the need for high-impact exercise.
10 citations
TL;DR: The role of PTHrP in the normal mammary gland and its contributions to breast pathogenesis are focused on and may play a role in regulating neonatal bone and mineral metabolism.
Abstract: Parathyroid hormone-related protein (PTHrP) signaling has been shown to affect the development of many tissues including bone, cartilage, and mammary gland. In this review, we focus on the role of PTHrP in the normal mammary gland and its contributions to breast pathogenesis. During embryonic mammary development, PTHrP drives mammary mesenchyme specification, which is responsible for maintaining mammary cell fate, promoting the outgrowth of ducts, and directing the formation of the nipple. During lactation, PTHrP mobilizes maternal calcium to ensure a supply of calcium into milk and may play a role in regulating neonatal bone and mineral metabolism. PTHrP is expressed in primary breast cancer and breast cancer metastases, and contributes to the formation of osteolytic bone lesions as well as the growth and progression of primary tumors.
9 citations
TL;DR: This review focuses on one such humoral factor produced by osteocytes, fibroblast growth factor 23, and the involvement of this key phosphate-regulating hormone in human disease.
Abstract: Osteocytes have emerged as the principal controlling cell type in bone. It is now clear that osteocytes communicate with each other, with other key bone cell types and also function as a vital endocrine organ. In this review, we will focus on one such humoral factor produced by osteocytes, fibroblast growth factor 23 and the involvement of this key phosphate-regulating hormone in human disease.
9 citations
TL;DR: The intimate relationship between osteocytes and osteoclasts suggests that a better knowledge of the factors produced by osteocytes could lead to a better understanding of osteoclast formation and activity.
Abstract: Osteoclasts strongly contribute to proper bone quality and function. Their actions are largely coordinated by osteocytes, i.e., osteocytes devoid of mechanical stimuli produce a multitude of membrane bound and soluble factors that stimulate the formation of osteoclasts. Among these are inflammatory factors, the most well known being receptor activator of nuclear factor κB ligand, matricellular proteins, and growth factors/morphogens such as WNTs. The intimate relationship between osteocytes and osteoclasts suggests that a better knowledge of the factors produced by osteocytes could lead to a better understanding of osteoclast formation and activity.
6 citations
TL;DR: New genetic tools in mice will allow genes of interest to be inactivated in experimentally defined contexts, thus allowing investigators to distinguish direct effects on each tissue from physiological responses to a primary phenotype in the other.
Abstract: Bone and muscle mass are highly correlated. In part, this is a consequence of both tissues sharing common genetic determinants. In addition, both tissues are responsive to their mechanical environments. New genetic tools in mice will allow genes of interest to be inactivated in experimentally defined contexts, thus allowing investigators to distinguish direct effects on each tissue from physiological responses to a primary phenotype in the other.
TL;DR: There is no hard data available to support the effectiveness of this treatment in the reduction in fragility fractures or kidney stone incidence, but a novel treatment approach would be the use of effervescent potassium calcium citrate that not only prevents complications of bone loss but may diminish the risk of kidney stone formation.
Abstract: With the increasing epidemic of obesity in the United States as well as abroad, bariatric surgery has emerged as the most effective and sustained treatment for reduction. This treatment modality has been well recognized to diminish the risk of cardiovascular morbidity and mortality and ameliorate diabetes mellitus. However, with time, derangement in mineral metabolism has emerged as a major complication in this population. Population-based study has shown increased prevalence of bone fractures and kidney stone formation following bariatric surgery. The risk appears to be more specific after Roux-en-Y gastric bypass procedures, the most common surgical approach among this population. Over the past decade, there have been advances in the understanding of pathophysiologic mechanisms of both bone loss and kidney stone disease in these patients. The understanding of these underlying pathophysiologic mechanisms may lead to the development of drug therapies that ameliorate this complication. Unfortunately, at the present time, there is no hard data on any specific treatment showing decreased incidence of fragility fractures or kidney stone passage. However, some studies suggest that calcium and vitamin D supplementation may decrease bone loss and bone turnover, and as a result, increase bone mineral density in this population. However, there is concern with the development of kidney stone formation following such an approach. A novel treatment approach would be the use of effervescent potassium calcium citrate that not only prevents complications of bone loss but may diminish the risk of kidney stone formation. Despite preliminary results showing the effectiveness of this drug in the reduction in the parathyroid hormone, bone turnover, and improvement in the urinary saturation marker showing effectiveness against calcium oxalate and uric acid stones, there is no hard data available to support the effectiveness of this treatment in the reduction in fragility fractures or kidney stone incidence. Such studies to explore this effect must be considered in the future.
TL;DR: The role of parathyroid hormone-related protein (PTHrP) and its mode of action on pancreatic beta-cell function, proliferation, and survival in rodents as well as in human beta-cells is enumerated.
Abstract: Diabetes is one of the fastest growing diseases worldwide, with an immense economic and health burden attached. It is now well accepted that a deficiency of functional insulin-producing pancreatic beta-cells is the main cause for all forms of diabetes. Several approaches are being taken to increase functional beta-cell mass. These include differentiation of new beta-cells from stem cells or progenitor cells, transdifferentiation of beta-cells from other mature cell types, as well as finding ways to enhance the function, proliferation, survival, and regeneration of preexisting beta-cells. This article enumerates on the role of parathyroid hormone-related protein (PTHrP) and its mode of action on pancreatic beta-cell function, proliferation, and survival in rodents as well as in human beta-cells. A further understanding of the mechanism of action of PTHrP and its role in the normal physiology and pathophysiology of the beta-cell will be important for its potential use in future as a therapeutic treatment for diabetes.
TL;DR: A better understanding of the mechanisms whereby PTH/PTHrP signaling impacts the cardiovascular system will provide therapeutic insights useful for treating patients afflicted with heart failure, chronic kidney disease-mineral and bone disorder, and diabetic arteriosclerosis.
Abstract: All calciotropic hormones have vasculotropic actions. This terse tenet challenges us to re-think the roles played by the PTH/PTHrP receptor (PTH1R) in vertebrate physiology. PTH1R signaling does not only control bone formation and serum calcium phosphate homeostasis. Cues dependent upon the PTH1R maintain myocardial viability during prenatal development and regulate arteriosclerotic calcification and vascular remodeling during post-natal life. A better understanding of the mechanisms whereby PTH/PTHrP signaling impacts the cardiovascular system will provide therapeutic insights useful for treating patients afflicted with heart failure, chronic kidney disease-mineral and bone disorder, and diabetic arteriosclerosis.
TL;DR: The causal role of PTHrP in humoral hypercalcemia of malignancy and its local involvement in the progression of osteolytic and osteoblastic cancer bone metastases are summarized and therapeutic opportunities and limitations to targeting P THrP directly and indirectly in cancer patients are examined.
Abstract: Since its discovery as the principal mediator of humoral hypercalcemia of malignancy, parathyroid hormone-related protein (PTHrP) has emerged as a key player in skeletal complications associated with solid tumor metastasis to bone. In addition to functioning as an endocrine factor, this pleiotropic peptide mediates its actions locally on tumor and stromal cells in paracrine, autocrine, and intracrine fashion when cancer metastasizes to the bone compartment. Multiple splice variants and newly described PTHrP fragments confer diverse functions to PTHrP that extend beyond binding to its common receptor with parathyroid hormone. Here, we summarize the causal role of PTHrP in humoral hypercalcemia of malignancy and its local involvement in the progression of osteolytic and osteoblastic cancer bone metastases. Clinical and preclinical findings describing how PTHrP regulates tumor and stromal cell interactions are summarized, with emphasis on emerging evidence of PTHrP’s role in tumorigenesis and cancer cell proliferation. Finally, we examine therapeutic opportunities and limitations to targeting PTHrP directly and indirectly in cancer patients.
TL;DR: The frequency of bariatric operations is rising rapidly as is the number of patients on long term follow-up, therefore, it is important to study the nutritional and metabolic complications and establish preventive measures.
Abstract: The frequency of bariatric operations is rising rapidly as is the number of patients on long term follow-up. Therefore, it is important to study the nutritional and metabolic complications and establish preventive measures. Secondary hyperparathyroidism and metabolic bone disease are frequent after bariatric surgery and are caused by the reduced intake and absorption of calcium and vitamin D. Unfortunately, obesity itself poses a risk of vitamin D deficiency and secondary hyperparathyroidism, other risk factors being darker skin colour, increasing age and living at high latitude. These risks are further increased by bariatric surgery the type of operation being the most important risk factor. Purely restrictive operations carry the lowest risk, reduced calcium intake being the main cause for secondary hyperparathyroidism. In malabsorptive operations calcium and vitamin D malabsorption further increase the risk of secondary hyperparathyroidism and osteoporosis. Prevention can be efficiently established by supplementation with calcium and vitamin D dosed according to the degree of malabsorption.
TL;DR: The gene regulatory network underlying the actions of PTHrP and Ihh needs to be understood through combinatorial approaches to genome-wide analyses and mouse genetics, which will open a new avenue for the application of the Ihh-P THrP negative feedback system to the treatment of skeletal disorders.
Abstract: Parathyroid hormone-related protein (PTHrP) was initially identified as a humoral factor that causes the humoral hypercalcemia of malignancies. PTHrP is expressed in tumors and a variety of tissues, acting on the formation and maintenance of these tissues in a paracrine manner. Skeletal formation is one of the notable developmental events in which PTHrP acts as a master regulator. During endochondral ossification, PTHrP is expressed in periarticular regions of fetal cartilage (also referred to as the growth plate) and the perichondrium, whereas the PTH/PTHrP receptor (PPR) is expressed strongly in pre-hypertrophic chondrocytes and weakly in columnar proliferating chondrocytes. Genetic studies have revealed that PTHrP-PPR signaling regulates the differentiation of chondrocytes to maintain a certain length of the growth plate via a negative feedback loop with Indian hedgehog (Ihh) expressed in pre-hypertrophic and hypertrophic chondrocytes. The Ihh-PTHrP negative feedback loop is central to the proper growth of endochondral skeletons. Ihh also exerts a PTHrP-independent function during endochondral ossification; it directly stimulates chondrocyte proliferation and differentiates progenitors into osteoblasts, the bone-forming cells. To further extend our knowledge of the Ihh-PTHrP negative feedback loop, we need to understand the gene regulatory network underlying the actions of PTHrP and Ihh through combinatorial approaches to genome-wide analyses and mouse genetics, which will open a new avenue for the application of the Ihh-PTHrP negative feedback system to the treatment of skeletal disorders.
TL;DR: A comprehensive look back at the origins of the science as well as the severe metabolic complications that furthered understanding, prompted innovative medical and surgical approaches, and ultimately led to modern day practice is looked back at.
Abstract: In the past 100 years, there have been myriad medical discoveries—giant steps—from Louis Pasteur’s germ theory, to the understanding of gut physiology and metabolic processes—that are the essential underpinnings of modern day medicine. The beginnings of surgery to promote weight loss, now known as bariatric surgery, date back to the 1880s when it was noted that gut resections resulted in weight loss. It was not long afterward that articles started to appear documenting nutritional “disturbances” and the patient’s likelihood of survival based upon the location and the length of bowel removed. Numerous articles have been penned citing the first bariatric surgeries, but to date, there has not been a comprehensive look back at the origins of the science as well as the severe metabolic complications that furthered understanding, prompted innovative medical and surgical approaches, and ultimately led to modern day practice. This article endeavors to do exactly that. Intestinal bypass surgeries to treat obesity are here to stay. Some of the most profound complications of intestinal bypass manifest in the skeleton and include skeletal demineralization, hyperoxaluria, nephrolithiasis, and fractures. Much has been done to further elucidate the underlying mechanisms, identify preventive strategies, and implement practice guidelines, but this patient population remains at increased risk for metabolic bone disease.
TL;DR: Despite current limitations, muscle–bone strength indicators have been defined that can already be used today in order to differentiate primary and secondary bone disorders thus underlining the validity of the “muscle–bone” approach.
Abstract: The ontogenetic adaptation of bones to their habitual loads offers a rationale for imaging muscle–bone relationships. Provided that bones adapt to strains that are chiefly determined by muscle contractions, information from muscle and bone scans allows comparing measures of bone stiffness and strength with surrogate measures for muscular force generation. Prediction of the mechanical behavior of bone is nowadays well possible by peripheral quantitative computed tomography (pQCT). However, prediction of muscle forces is not currently feasible. pQCT offers the opportunity to outline gross muscle cross-sectional area (CSA) as a surrogate measure of the force-generating capacity of muscle groups. Ultrasound and magnetic resonance (MR) imaging allow identification of single muscles. In addition, ultrasound also offers the possibility to assess muscle architecture and thus to assess physiological CSA as a more likely predictor of muscle forces than anatomical CSA. Although there is currently no single technique in use to simultaneously assess muscle volume, CSA, and architecture at the level of single muscles, this could in future be possible by MR diffusion imaging. Current attempts to quantify muscle “quality” are not directly related to the force-generating capacity and thus only of indirect help. Hence, one should hope that better imaging assessments of muscle will be possible in future. However, despite these current limitations, muscle–bone strength indicators have been defined that can already be used today in order to differentiate primary and secondary bone disorders thus underlining the validity of the “muscle–bone” approach.
TL;DR: P THrP has been localized in fish neoplasms suggesting that PTHrP’s role in tumor formation is a conserved role from at least fish to humans and a comparison among the analogous human, mouse, chicken, xenopus, and fugu sequences demonstrates elements of conservation.
Abstract: After the discovery of parathyroid hormone-related protein (PTHrP) as the cause of the hypercalcemia of malignancy, it was found to be distributed widely in tissues, with its actions driving many physiologic and pathologic conditions. Its involvement in cancer extended to a contribution to the ability of cancer cells to promote bone resorption and establish as metastases. It was found to have multiple activities within the sequence, including a nuclear localizing sequence and a specific nuclear transport system. PTHrP and parathyroid hormone (PTH) appear to have arisen from a common ancestral gene and the comparative endocrinology and genomics studies focused on finding where the two genes appeared. PTHrP has been identified in bony and cartilaginous fish in the same tissues as in humans, indicating that PTHrP has fundamental and basic physiological roles in all vertebrates. PTHrP has been localized in fish neoplasms suggesting that PTHrP’s role in tumor formation is a conserved role from at least fish to humans. Interestingly, PTH has been identified in both bony and cartilaginous fish even though they lack a parathyroid gland and indicate that PTH’s evolutionary history is much longer too. So the point where PTHrP and PTH were duplicated is still unknown. A comparison among the analogous human, mouse, chicken, xenopus, and fugu sequences of the PTHrP gene demonstrates elements of conservation. When coupled with human Encode data and knowledge of interspecies gene structure, it offers rudimentary insights into function and underwrites hypotheses on physiology.
TL;DR: Significant weight loss after gastric bypass surgery is associated with an increase in serum 25-hydroxy vitamin D levels; however, the effect is small, and thus supplementation remains the mainstay of treatment and prevention of vitamin D deficiency in this population.
Abstract: Vitamin D deficiency is common after Roux-en-Y gastric bypass surgery, as malabsorptive component of the procedure affects its absorption, and dietary intake is inadequate due to restricted postoperative diet. Obesity itself is associated with low 25-hydroxy vitamin D levels due to larger volume of distribution with increased body fat mass, and studies have confirmed the presence of fat-soluble vitamin D in human adipose tissue. Massive weight loss after gastric bypass surgery is associated with an increase in serum 25-hydroxy vitamin D levels; however, the effect is small, and thus supplementation remains the mainstay of treatment and prevention of vitamin D deficiency in this population. Higher doses of vitamin D are often required, as most patients remain obese after bariatric surgery, and its absorption is reduced. Guidelines recommended supplementing bariatric patients with at least 3,000 IU per day of vitamin D, while doses as high as 50,000 IU 1–3 times weekly may be required in some patients.