Effect of Potassium Citrate on Bone Density, Microarchitecture, and Fracture Risk in Healthy Older Adults without Osteoporosis: A Randomized Controlled Trial

Jehle, Sigrid; Hulter, Henry N.; Krapf, Reto

doi:10.1210/jc.2012-3099

Cited by 135 publications

(118 citation statements)

References 43 publications

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“…The finding in rats that prolonged overt CMA results in a selective loss of cortical bone mass contrasts with the results of a recent randomized placebo-controlled trial in elderly normal humans, in which low-grade CMA induced by the Western diet was neutralized with prolonged K citrate treatment (13). In the human study, neutralization of the dietary acid load resulted in a large and significant improvement in total vBMD, net of placebo, but the improved vBMD was fully accounted for by increased trabecular vBMD.…”

Section: Discussioncontrasting

confidence: 87%

Effect of chronic metabolic acidosis on bone density and bone architecture in vivo in rats

Gasser

Hulter

Imboden

et al. 2014

American Journal of Physiology-Renal Physiology

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Gasser JA, Hulter HN, Imboden P, Krapf R. Effect of chronic metabolic acidosis on bone density and bone architecture in vivo in rats. Am J Physiol Renal Physiol 306: F517-F524, 2014. First published December 19, 2013 doi:10.1152/ajprenal.00494.2013.-Chronic metabolic acidosis (CMA) might result in a decrease in vivo in bone mass based on its reported in vitro inhibition of bone mineralization, bone formation, or stimulation of bone resorption, but such data, in the absence of other disorders, have not been reported. CMA also results in negative nitrogen balance, which might decrease skeletal muscle mass. This study analyzed the net in vivo effects of CMA's cellular and physicochemical processes on bone turnover, trabecular and cortical bone density, and bone microarchitecture using both peripheral quantitative computed tomography and CT. CMA induced by NH4Cl administration (15 mEq/kg body wt/day) in intact and ovariectomized (OVX) rats resulted in stable CMA (mean ⌬ [HCO 3 Ϫ ]p ϭ 10 mmol/l). CMA decreased plasma osteocalcin and increased TRAP5b in intact and OVX animals. CMA decreased total volumetric bone mineral density (vBMD) after 6 and 10 wk (week 10: intact normal ϩ2.1 Ϯ 0.9% vs. intact acidosis Ϫ3.6 Ϯ 1.2%, P Ͻ 0.001), an effect attributable to a decrease in cortical thickness and, thus, cortical bone mass (no significant effect on cancellous vBMD, week 10) attributed to an increase in endosteal bone resorption (nominally increased endosteal circumference). Trabecular bone volume (BV/TV) decreased significantly in both CMA groups at 6 and 10 wk, associated with a decrease in trabecular number. CMA significantly decreased muscle cross-sectional area in the proximal hindlimb at 6 and 10 wk. In conclusion, chronic metabolic acidosis induces a large decrease in cortical bone mass (a prime determinant of bone fragility) in intact and OVX rats and impairs bone microarchitecture characterized by a decrease in trabecular number. osteoporosis; mineral density; metabolic acidosis; overiectomy CHRONIC METABOLIC ACIDOSIS (CMA) is one of the cardinal acidbase disorders, characterized by a primary decrease in body base content and diagnosed clinically by measuring decreased plasma [HCO 3 Ϫ ] and blood pH. The disorder can be caused by increased production or decreased elimination of protons (such as in organic forms of metabolic acidosis or chronic renal failure) or by base losses (such as intestinal bicarbonate loss in diarrhea or bicarbonaturia in proximal tubular acidosis). Metabolic acidosis is regarded as the most common acid-base disorder due to the high worldwide prevalence of chronic diarrheal disease.Bone serves as an important proton buffer in metabolic acidosis and, thus, exhibits a homeostatic role by attenuating the severity of metabolic acidosis. Bone exposed to acidic media in vitro undergoes physicochemical mineral dissolution leading to a fall in mineral sodium, potassium, carbonate, calcium, and phosphate. In this process, calcium released from the bone leads to hypercalciuria, the magnitude of w...

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Section: Discussioncontrasting

confidence: 87%

Effect of chronic metabolic acidosis on bone density and bone architecture in vivo in rats

Gasser

Hulter

Imboden

et al. 2014

American Journal of Physiology-Renal Physiology

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“…Those speculations of Dawson-Hughes et al [23] and Jehle et al [24] accorded with our earlier studies showing that administration of potassium bicarbonate in doses up to 120 milliequivalents per day both decrease markers of bone resorption and increased markers of bone formation [30].…”

Section: Clues Inspiring the Hypothesissupporting

confidence: 66%

“…A study by Jehle et al in elderly but not osteoporotic women resulted in slightly negative net endogenous acid production rates by some participants and in those participants the best skeletal responses were observed [24]. Indeed, the authors of that study speculated that ''.…”

Section: Clues Inspiring the Hypothesismentioning

confidence: 95%

“…Although research relating to acid-base physiology and bone health in humans remains active in the 21st century [14,19,[22][23][24][25][26], its conceptual emphasis has been unidirectional in respect of acid-base balance. The cumulative evidence that chronic metabolic acidosis induces resorptive bone mass loss dominated the thinking on acid-base and bone, directing research toward reducing the net endogenous acid production's bone resorptive effect.…”

Section: Comments On Hypothesismentioning

confidence: 99%

“…Current therapeutic approaches for osteoporosis, however, never explicitly consider the alkali supply requirements for osteoblastic bone formation. Some studies have shown that alkali administration as supplement or as alkalinizing whole foods can improve skeletal health in terms of favorable changes in markers of bone formation and/or resorption, or improvements in bone mineral density [23][24][25]30]. But in those studies the objectives were to reduce the rate of endogenous non-carbonic acid production and reduce the degree of attendant metabolic acidosis.…”

Section: Basis Of the Hypothesismentioning

confidence: 99%

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A neglected requirement for optimizing treatment of age-related osteoporosis: Replenishing the skeleton’s base reservoir with net base-producing diets

Sebastián

Frassetto

2016

Medical Hypotheses

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a b s t r a c tOsteoporosis is a disorder of bone in which the mass of the bone is reduced and the bone's architecture at the microscopic level is disordered. Together those abnormalities predispose affected individuals to experience fractures despite only minimal trauma (i.e., fragility fractures). Age related osteoporosis is a common type of osteoporosis that occurs with aging in both men and women usually beginning after the age of peak bone mass. Research has found that the disorder can be partially reversed by reducing the net amount of acid that is produced when consuming typical Western diets. However, the amelioration that results has not been so dramatic or so consistent that physicians have adopted the procedure as part of the standard treatment for age-related osteoporosis. We propose that reducing the net acid load from the diet is not sufficient to reverse age related osteoporosis because it fails to supply base needed to restore the large amount of base in bone that had been lost by reacting with the net acid load of the diet that had been consumed for years or decades. Reducing the net acid load from the diet might be expected to have little ameliorative effect or merely slow the progression of the disorder. We hypothesize that both to restore osteoporotic bone to, or nearly to, its pre-disease state, as well as to eliminate the risk of fragility fractures, requires consuming diets that produce net amounts of base to restore the base lost from years to decades of consuming diets that produce net amounts of acid. We hypothesize also that the excess base and attendant subclinical metabolic alkalosis will both stimulate the cellular process of bone formation and suppress the cellular process of bone resorption, and thereby implement the restorative process.Ó 2016 Elsevier Ltd. All rights reserved. Introduction Functions of the skeletonThe human skeleton is an adaptive, self-organizing, multifunctional organ-system vital to human health. It functions (a) as a structure supporting body movement through connections with skeletal muscles, and as trauma-defense through its structural surrounding of vital organs, (b) it contributes to cellular oxygenation throughout the body by generating and distributing red blood cells systemically via the circulation; (c) it contributes to systemic calcium and phosphorus homeostasis in virtue of its large reservoir of labile calcium and phosphorus; (d) it contributes to systemic acid-base homeostasis in virtue of its large reservoir of labile base equivalents residing in calcium hydroxyapatite, the major mineral component of bone; and, (e) contributes to the integration of body physiology through two-way endocrine communication with numerous organ systems of the body (pp. 3-4 [1]) (p. 3 [2]). Each subsystem of the human skeleton adapts to changing environmental conditions-rendering the skeleton a complex adaptive system. Bone remodelingThroughout one's life the skeleton continually remodels itself in response to changing mechanical loads and mechanical microdamage, thro...

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Neurochemical Effects of Western Diet Consumption on Human Brain

Farooqui

2015

Diet and Exercise in Cognitive Function and Neurological Diseases

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Effect of Potassium Citrate on Bone Density, Microarchitecture, and Fracture Risk in Healthy Older Adults without Osteoporosis: A Randomized Controlled Trial

Cited by 135 publications

References 43 publications

Effect of chronic metabolic acidosis on bone density and bone architecture in vivo in rats

Effect of chronic metabolic acidosis on bone density and bone architecture in vivo in rats

A neglected requirement for optimizing treatment of age-related osteoporosis: Replenishing the skeleton’s base reservoir with net base-producing diets

Neurochemical Effects of Western Diet Consumption on Human Brain

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