No changes in levels of bone formation and resorption markers following a broad-spectrum antibiotic course

Abstract

BackgroundIntestinal bacteria influence bone remodeling in rodents, and antibiotic manipulation of the rodent gut microbiota increases bone formation and prevents ovariectomy-induced bone loss. In theory, these effects may be mediated by changes in sex hormone biotransformation in the gut, gut serotonin secretion or nutrition-induced secretion of glucagon-like peptide 2 (GLP-2) and glucose-dependent insulinotropic hormone (GIP). Antibiotics change the human gut microbiota, but the effect of antibiotic treatment on human bone turnover is unknown.MethodsWe analyzed serum levels of bone turnover markers, serotonin, GLP-2 and sex hormones before, immediately after, and eight, 42 and 180 days after a 4-day per oral antibiotic cocktail (vancomycin 500 mg, gentamycin 40 mg and meropenem 500 mg once-daily) in twelve healthy adult males. Fasting and meal-stimulated procollagen type I amino-terminal propeptide (P1NP), C-telopeptide of type I collagen (CTX) and osteocalcin levels were measured.ResultsWhile the antibiotic course reduced the stool abundance and composition of anaerobic bacteria as confirmed by cultivation studies, neither short nor long-term alterations in serum P1NP, CTX and osteocalcin were observed. Furthermore, we did not observe any changes in levels of serum GLP-2, serotonin or sex hormones.ConclusionEradication of anaerobic bacteria from healthy adult males had no effect on serum bone turnover markers.

Analysis of the Associations Between the Human Fecal Microbiome and Bone Density, Structure, and Strength: The Osteoporotic Fractures in Men (MrOS) Cohort

“…Similarly, antibiotic treatments have been shown to have a range of effects on bone density; antibiotic-treated mice appear to have higher bone density in some experiments, (12) but other reports include adverse (15,16) or no effects. (17) Finally, a number of experiments have demonstrated that probiotic preparations, commonly including one or more Lactobacillus species, may positively affect mineral metabolism or bone health. (18)(19)(20)(21) Despite the growing series of animal experiments that demonstrate an effect of the gut microbiome on skeletal health, there are very few studies in humans that examine whether there are associations between the gut microbiome and skeletal status.…”

“…Similarly, antibiotic treatments have been shown to have a range of effects on bone density; antibiotic‐treated mice appear to have higher bone density in some experiments, ( 12 ) but other reports include adverse ( 15,16 ) or no effects. ( 17 ) Finally, a number of experiments have demonstrated that probiotic preparations, commonly including one or more Lactobacillus species, may positively affect mineral metabolism or bone health. ( 18‐21 )…”

Bone mineral as a drug-seeking moiety and a waste dump

“… 42 , 43 Even without the use of a carrier, prolonged use of antibiotics such as gentamycin or vancomycin have been reported to have no impact on bone turnover markers such as carboxy-terminal collagen crosslinks (CTX) or osteocalcin in humans. 45 We have not been able to find any studies reporting a negative effect of long-term antibiotic usage or accumulation in bone with the exception of tetracycline. Recurrence of infection is reduced both in chronic osteomyelitis as well as in PJI, both with non-HA-binding antibiotics such as penicillin 46 or with HA-binding antibiotics such as rifampicin, 47 even with prolonged treatment.…”

“Osteomicrobiology”: The Nexus Between Bone and Bugs

“…Another study showed that low dose administration of penicillin enhanced the BMD and bone mineral content (BMC) of female C57BL/6J mice ( Cox et al, 2014 ). However, in humans administration of broad spectrum antibiotics did not show any affect on bone health ( Mikkelsen et al, 2018 ).…”