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MyDeficiencies

Abaloparatide

parathyroid hormone-related protein (PTHrP) analog, PTH1 receptor agonist, bone anabolic

Also sold as Tymlos, Eladynos.

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Findings for this medication

Research about this medication, graded for how strongly each finding can be attributed to it. Nothing here describes your own levels.

Abaloparatide has essentially no classical depletion machinery. It is a 34-amino-acid peptide given by subcutaneous injection, cleared by non-specific proteolytic degradation, not metabolized by any CYP450 enzyme, does not induce or inhibit any CYP450 enzyme, and is not a substrate of the renal transporters OAT1, OAT3, OCT2, MATE1, or MATE2K. Because it bypasses the gut entirely, none of the chelation, gastric-pH, or absorption-competition mechanisms that drive most oral-drug nutrient depletions apply. Its real nutrient signal instead comes directly from its own intended pharmacology: it selectively activates the PTH1 receptor, reproducing core parathyroid hormone actions on the calcium, phosphate, and vitamin D axis. That signal is unambiguous and clinically documented at scale for calcium: the regulatory label reports hypercalcemia in 3% of abaloparatide-treated postmenopausal women versus 0.1% on placebo, the pivotal ACTIVE trial found hypercalcemia in 3.4% of abaloparatide patients versus 6.4% on teriparatide (risk difference -2.96, P=.006), and the ATOM trial in men found hypercalcemia in 1.3% of abaloparatide patients versus none on placebo. This is graded red. The label's own animal toxicology data (rats and monkeys) document a real, dose-related decrease in serum phosphorus alongside the calcium rise, and a drug-specific rat study (Yang et al, Endocrinology 2023) found abaloparatide significantly raises 1,25-dihydroxyvitamin D and osteocalcin while leaving blood calcium unaffected at a lower dose, a genuine axis-shift finding graded orange under a combined Phosphate and vitamin D entry. A third, independently documented label finding, a rise in serum uric acid above the normal range in 25% of women and 7% of men (versus 6% each on placebo), with no corresponding rise in gout, is also graded orange.

parathyroid hormone-related protein (PTHrP) analog, PTH1 receptor agonist, bone anabolic · ATC H05AA04 · also sold as Tymlos and Eladynos · reviewed 2026-09-28. This describes research about the medication. It does not say anything about your own levels or health.

How to read the evidence grades

These colours describe how strongly a finding can be attributed to the medication in the research. They are not a severity score and they say nothing about your own health.

Grades describe how strongly a finding can be attributed to Abaloparatide in the research — not how common it is, how serious it would be, and not anything about you personally.

Red — Severe
Two or more independent Tier A sources, this drug in the cohort, the nutrient directly measured, consistent direction, clinically meaningful magnitude, a named mechanism, no substantial contradicting Tier A evidence.
Orange — Moderate
At least one Tier A source with this drug in the cohort showing a real but bounded deficit: an exposure window, a subgroup, low frequency, or a functional rather than circulating deficit.
Yellow — Low
Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction.
Not graded — disclosed evidence gap
Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result.Source definition: Not gradeable under the rules above because nothing has been measured. Published as a documented gap, never as reassurance that there is no effect.

What the research found

Calcium, frequent, dose-related hypercalcemia confirmed in three independent trial populations

Red — Severe

See study details

Abaloparatide reliably raises serum calcium above the normal range in a small but consistent minority of treated patients across three separate trial populations, through a well-characterized PTH1-receptor mechanism.

Full detail, limits and 1 references

What the grade means here: Two or more independent Tier A sources, this drug in the cohort, the nutrient directly measured, consistent direction, clinically meaningful magnitude, a named mechanism, no substantial contradicting Tier A evidence. Red

Limits on what this shows

  • Key negative/null findings: In the same Yang et al rat study, the 40 mcg/kg/day abaloparatide dose used did not itself raise blood calcium despite raising 1,25(OH)2D and osteocalcin, which the authors interpret as evidence that the 1,25(OH)2D/osteocalcin pathway helps buffer calcium at that specific dose and duration; this null finding is reported here rather than omitted, though it does not contradict the much larger, dose-relevant human hypercalcemia signal above.
  • At-risk subgroups: Mild or moderate renal impairment (hypercalcemia incidence 4% versus 1% with normal renal function, per label); patients with pre-existing hypercalcemic disorders (contraindicated by label recommendation); by mechanism, patients also taking calcium or vitamin D supplementation above the trial-tested range.
  • Counter-evidence on record: None found contradicting direction or the general low-single-digit-percent frequency; the ACTIVE trial's active-comparator design (versus teriparatide) is itself the main limitation on that specific data point, disclosed above rather than treated as a placebo-equivalent result.

Regulatory status

Label states abaloparatide "may cause hypercalcemia" and is "not recommended in patients with pre-existing hypercalcemia or in patients who have an underlying hypercalcemic disorder, such as primary hyperparathyroidism." Hypercalcemia is defined in the label as albumin-corrected serum calcium ≥10.7 mg/dL at 4 hours post-injection.

Population evidence

Three independent Tier A sources, all with abaloparatide in the studied cohort. (1) DailyMed/FDA label, pivotal postmenopausal osteoporosis trial: hypercalcemia in 3% of abaloparatide-treated women versus 0.1% on placebo. (2) ACTIVE trial (JAMA 2016, randomized, double-blind, 2,463 women, 18 months, 28 sites/10 countries): hypercalcemia in 3.4% of abaloparatide patients (28 of 820) versus 6.4% on teriparatide (52 of 816), risk difference -2.96 (P=.006); an active-comparator finding, so it does not by itself test abaloparatide against non-use, but it independently confirms the direction and approximate magnitude found in the placebo-controlled label data. (3) ATOM trial (men, randomized, double-blind, placebo-controlled, 228 men, 12 months): hypercalcemia in 1.3% of abaloparatide-treated men (2 of 149) versus none on placebo.

Mechanism

Named: PTH1-receptor activation directly increases distal renal tubular calcium reabsorption (NCBI Bookshelf PTH physiology reference) and increases bone-resorption-linked calcium release; a drug-specific rat study (Yang et al, Endocrinology 2023, n=8, abaloparatide 40 mcg/kg/day SC for 7 days) additionally found abaloparatide raises blood 1,25-dihydroxyvitamin D and carboxylated osteocalcin (Gla-Ocn), proposing a 1,25(OH)2D/osteocalcin signaling contribution alongside the direct renal and skeletal routes (see Phosphate and vitamin D axis entry; shared source, see Overlap map).

Counter-evidence held on record

This is an excess-direction, not a depletion-direction, finding: it must never be used to suggest increasing calcium intake beyond the label's own supplemental range (500-1000 mg calcium, 400-800 IU vitamin D daily, used in trials, both well under the NIH Office of Dietary Supplements adult tolerable upper intake levels of 2000-2500 mg calcium and 4000 IU vitamin D), and any calcium-related question belongs with the prescriber, not with a supplementation prompt.

Phosphate and vitamin D axis, animal-confirmed phosphate decrease, drug-specific vitamin D increase, mixed direction

Orange — Moderate

See study details

Abaloparatide's own regulatory label documents a dose-related serum phosphorus decrease in animal toxicology studies, and a drug-specific rat study independently found abaloparatide raises active 1,25-dihydroxyvitamin D, a real but bounded, mixed-direction axis effect with no confirmed human phosphate data yet.

Full detail and limits

What the grade means here: At least one Tier A source with this drug in the cohort showing a real but bounded deficit: an exposure window, a subgroup, low frequency, or a functional rather than circulating deficit. Orange

Limits on what this shows

  • Key negative/null findings: No phosphate measurement was reported in the Yang et al rat study; no human trial reviewed reported an on-treatment serum phosphate change, positive or null, so the phosphate side of this entry rests on animal toxicology data alone and is bounded accordingly. Total 25-hydroxyvitamin D (storage form) was not measured in the rat study, so this entry cannot state whether storage vitamin D falls in parallel with the active-hormone rise, unlike the corresponding teriparatide finding (see Overlap map and Sources).
  • At-risk subgroups: Not established in humans for phosphate; by mechanism, patients with baseline low-normal phosphate or concurrent phosphate-lowering therapy would be the plausible higher-risk group.
  • Counter-evidence on record: The vitamin D finding runs in a retention/increase direction, not depletion, and is itself evidence against a net vitamin D deficit; the phosphate finding's animal-toxicology-only status is its own bounding limitation, disclosed rather than extrapolated to humans.

Regulatory status

Label, Nonclinical Toxicology section (13.2): "In toxicity studies in rats and monkeys of up to 26-week and 39-week duration, respectively, findings included vasodilation, increases in serum calcium, decreases in serum phosphorus, and soft tissue mineralization at doses ≥10 mcg/kg/day." No phosphate-specific human monitoring requirement is stated; the ATOM (men's) trial required serum phosphorus to be within the normal range for eligibility but did not report on-treatment phosphate change.

Population evidence

Phosphate: Tier A, animal toxicology only (rats and monkeys, doses ≥10 mcg/kg/day, well above the fixed clinical 80 mcg dose on a per-kg basis for a typical adult); no human circulating phosphate change was found in either pivotal human trial reviewed. Vitamin D: Tier B, drug-specific. Yang et al, Endocrinology 2023: intact male Sprague-Dawley rats (n=8), abaloparatide 40 mcg/kg/day SC for 7 days versus vehicle. Blood 1,25-dihydroxyvitamin D significantly increased with abaloparatide (P<.01); carboxylated osteocalcin (Gla-Ocn) significantly increased (P<.01), uncarboxylated osteocalcin (Glu-Ocn) significantly increased to a lesser degree (P<.05), and the Gla-Ocn:Glu-Ocn ratio significantly increased (P<.01), with a significant positive correlation between 1,25(OH)2D and Gla-Ocn.

Mechanism

Named for both directions. Phosphate: PTH1-receptor activation "decreases phosphate reabsorption at the proximal convoluted tubule" (NCBI Bookshelf PTH physiology reference), standard endogenous PTH physiology reproduced by the drug. Vitamin D: PTH1-receptor activation stimulates renal 1-alpha-hydroxylase, converting storage 25-hydroxyvitamin D to active 1,25-dihydroxyvitamin D; the Yang et al authors further propose the resulting 1,25(OH)2D rise drives carboxylated-osteocalcin production as part of a calcium-buffering feedback loop.

Counter-evidence held on record

Do not present the vitamin D component as a depletion risk: the only drug-specific data found shows active 1,25-dihydroxyvitamin D rising, not falling, which is the expected, mechanistically anticipated direction for a PTH-axis drug and should never prompt additional vitamin D supplementation beyond the label's own baseline recommendation. Do not present the phosphate component as a confirmed human effect; it should surface only as a reason to keep phosphate within routine bone-metabolism monitoring, not as a supplementation prompt.

Uric acid, drug-specific elevation, larger in women, no downstream clinical effect observed

Orange — Moderate

See study details

Abaloparatide produces a real, drug-specific rise in serum uric acid above the normal range, substantially more often in the postmenopausal women's trial than in the men's trial, with no corresponding rise in gout or arthralgia in either.

Full detail and limits

What the grade means here: At least one Tier A source with this drug in the cohort showing a real but bounded deficit: an exposure window, a subgroup, low frequency, or a functional rather than circulating deficit. Orange

Limits on what this shows

  • Key negative/null findings: The label states directly, for both trial populations: "the hyperuricemia observed in TYMLOS-treated patients was not associated with an increase in adverse reactions of gout or arthralgia over that observed with placebo," the key bounding null finding for this entry.
  • At-risk subgroups: Not separately quantified; patients with pre-existing gout or hyperuricemia are the plausible, though unquantified, higher-risk group. The much larger effect size in the women's trial (25% versus 6%) versus the men's trial (7% versus 6%) is itself an unexplained sex-based difference worth flagging rather than averaging away.
  • Counter-evidence on record: The absence of a clinical gout signal in both trial populations is itself the counter-evidence limiting this entry's severity; the much smaller effect size in men versus women is also disclosed as a limitation on generalizing the women's-trial magnitude.

Regulatory status

Reported directly in the label's laboratory-findings text, separately for each pivotal trial population.

Population evidence

DailyMed/FDA label, two independent trial populations, both with abaloparatide in the cohort. Postmenopausal osteoporosis trial: among patients with normal baseline uric acid, 25% of the abaloparatide group versus 6% of the placebo group had at least one post-baseline concentration above the normal range. Male osteoporosis (ATOM) trial: among patients with normal baseline uric acid, 7% of the abaloparatide group versus 6% of the placebo group had at least one post-baseline concentration above the normal range, a much smaller effect size than in women.

Mechanism

Not elaborated in the label or in any source opened during this review. A plausible but unconfirmed route would run through PTH1-receptor effects on renal tubular urate handling, paralleling the confirmed effects on renal calcium and phosphate transport, but this specific pathway was not directly tested for abaloparatide or teriparatide in any source opened this session, so it is disclosed as unconfirmed rather than stated as established.

Counter-evidence held on record

This is an excess-direction, not a depletion-direction, finding and carries no established clinical consequence at approved dosing; it should surface only as a minor lab-monitoring note for patients with pre-existing gout, never as a supplementation or dietary-restriction prompt.

The five body-system areas

Each finding is counted once, in a single area. Where a study is mentioned in a second area it is context only.

Mitochondrial Burden

Each finding below is counted once, in this area only.

Mitochondrial burden, class extrapolation from teriparatide, tissue-specific osteoblast reprogramming, not abaloparatide-verified

Yellow — Low

See study details

No abaloparatide-specific mitochondrial study could be opened and verified this session; the entry is graded yellow purely as class extrapolation from a self-verified teriparatide (PTH 1-34) finding that PTH1-receptor signaling reprograms osteoblast energy metabolism toward glycolysis, which may or may not transfer to abaloparatide's distinct PTHrP-analog signaling profile.

Full detail, limits and 3 references

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow

Limits on what this shows

  • Key negative/null findings: None found either way for abaloparatide specifically; the class-level source itself reports no contradicting direction for teriparatide.
  • At-risk subgroups: Not applicable; a cell-type-specific, class-level, animal finding, not a patient subgroup risk.
  • Counter-evidence on record: None found; the entry's main caveat is that it rests entirely on class extrapolation from a different, though closely related, PTH1-receptor agonist, one step removed from its own primary source (review-mediated), and zero verified abaloparatide-specific evidence.

Regulatory status

Not addressed in labeling.

Population evidence

Abaloparatide-specific: a PubMed search-listing combining "abaloparatide" with "mitochondria" or "oxidative stress" returned one real, titled result, Wider et al, Journal of Clinical Medicine 2022, "Parathyroid Hormone-Related Peptide and Its Analog, Abaloparatide, Attenuate Lethal Myocardial Ischemia-Reperfusion Injury"; its abstract and full text could not be opened despite repeated attempts across multiple channels this session (see access note and Sources), so no abaloparatide-specific claim is made from it here. Class-level, self-verified this session: a narrative review (Journal of Bone and Mineral Research 2024, "Multifaceted roles of mitochondria in osteoblasts") states, quoted directly from the opened page, "Teriparatide, a widely prescribed bone anabolic protein consisting of amino acids 1 to 34 of human PTH, was shown to enhance bone formation by activating aerobic glycolysis and preventing glucose entry into the TCA cycle via IGF signaling in mouse osteoblasts" (its reference 44); the primary mouse study behind that citation was not independently opened this session, so this entry rests on the review's characterization only, exactly as the teriparatide sibling dossier also discloses.

Mechanism

Named at the class level only: IGF-signaling-mediated diversion of glucose from mitochondrial oxidative phosphorylation toward aerobic glycolysis in differentiating osteoblasts, described for PTH(1-34)/teriparatide specifically. Abaloparatide is a PTHrP(1-34) analog, not the PTH(1-34) molecule itself, and the label describes it only as a PTH1-receptor agonist activating cAMP signaling without the conformational or signaling-duration detail needed to confirm this mouse-osteoblast mechanism transfers identically; this uncertainty is disclosed rather than assumed away.

Counter-evidence held on record

This is a mechanism clarification about how a related drug builds bone in osteoblasts specifically, not a nutrient-style deficiency claim and not confirmed for abaloparatide itself; it must never be presented as evidence of systemic mitochondrial harm from abaloparatide or as a reason to recommend mitochondrial-support supplementation. Shares its underlying class-level source with the ATP production entry below; see Overlap map.

Oxidative Stress

Each finding below is counted once, in this area only.

Oxidative stress, class extrapolation from two self-verified teriparatide studies, protective direction, not abaloparatide-verified

Yellow — Low

See study details

No abaloparatide-specific oxidative-stress study could be opened this session; two independently self-verified, drug-specific teriparatide animal/cell studies found reduced oxidative-stress markers, a protective direction that is graded yellow here as class extrapolation only.

Full detail, limits and 1 references

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow

Limits on what this shows

  • Key negative/null findings: No human oxidative-stress-marker study in teriparatide-treated patients, and no abaloparatide study of any kind, was found or could be opened.
  • At-risk subgroups: Not applicable; a described benefit signal in disease models for a related drug, not a described risk for abaloparatide.
  • Counter-evidence on record: No study found showing teriparatide or PTHrP analogs worsening oxidative stress markers; the main limitation is the complete absence of abaloparatide-specific data and of human data for either drug on this question.

Regulatory status

Not addressed in labeling.

Population evidence

Abaloparatide-specific: same Wider et al 2022 title found but not opened, disclosed above; not used as evidence here. Class-level, both self-verified by directly opening the full text this session: (1) MLO-Y4 mouse osteocyte cells (teriparatide 10 nmol/L) and dexamethasone-induced-osteoporosis Sprague-Dawley rats (n=20, 10/group, intramuscular teriparatide): reactive oxygen species visibly reduced with teriparatide co-treatment versus dexamethasone alone; SOD2 mRNA (control 1.0±0.13, dexamethasone 0.42±0.11, dexamethasone+teriparatide 0.72±0.04, P<.05) and catalase mRNA (control 1.0±0.14, dexamethasone 0.37±0.17, dexamethasone+teriparatide 0.64±0.21, P<.05) both partially restored (PMC6594530). (2) 138 male Sprague-Dawley rats, spinal cord injury model, teriparatide 20 mcg/kg/day SC for up to 14 days (Frontiers in Pharmacology 2025): malondialdehyde fell (day 14: 0.42±0.03 versus saline 1.22±0.13, P<.001); glutathione peroxidase rose (0.5±0.03 versus 0.16±0.03, P<.001); Nrf2 rose (2.87±0.13 versus 0.82±0.06, P<.001) with elevated downstream HO-1 (251.42±2.72 versus 51.77±1.05, P<.001) and SOD2 (179.66±10.67 versus 10.16±1.15, P<.001); functional recovery (BBB score, open-field movement distance) also improved with teriparatide (P≤.015).

Mechanism

Named at the class level for teriparatide: study 1 proposes an AKT-pathway route suppressing apoptosis; study 2 identifies the Nrf2/HO-1 antioxidant-response pathway directly. Neither study used abaloparatide, and the same PTHrP-analog-versus-PTH(1-34) signaling-profile caveat noted in the Mitochondrial burden entry applies here too.

Counter-evidence held on record

This is a reverse-direction (protective) finding in a related drug's animal/cell models only, not confirmed for abaloparatide: it should never be presented as evidence that antioxidant supplementation is unnecessary during abaloparatide treatment, nor generalized to humans or to abaloparatide itself without direct confirmation.

  • PubMed search-listing queries: "abaloparatide copper," "abaloparatide iron," "abaloparatide microbiome OR microbiota OR gut bacteria," "abaloparatide hemoglobin OR hematocrit OR erythropoiesis," "abaloparatide ATP OR oxygen consumption OR energy metabolism," "abaloparatide mitochondria OR oxidative stress." — pubmed.ncbi.nlm.nih.gov search-listing pages (not individual abstract pages), each fetched and read directly, each returning either a confirmed explicit zero-result page or the single Wider et al 2022 title. Used to establish the Ungraded entries (Copper, Iron) and the genuine-versus-tooling-limited distinction described in the headline finding.

Copper and Iron Balance

Copper and iron are assessed separately. Nothing here is counted twice.

Copper

Not graded — disclosed evidence gap

See study details

No Tier B or C evidence, at either the abaloparatide-specific or the teriparatide/PTH-class level, and no circulating consumer claim, connecting abaloparatide to copper status was found.

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded

Limits on what this shows

  • Why no grade: The dual condition for ungraded is met. A PubMed search-listing query for "abaloparatide copper" returned a confirmed, explicit zero-result page ("No results were found... processed without automatic term mapping because it retrieved zero results"). The sibling teriparatide dossier in this same batch, searching the identical question for the class-level drug, independently reached the same ungraded conclusion for copper (via a Crossref query and multiple web-search phrasings), so no class-level lead exists either. A consumer-facing interactions/side-effects check (drugs.com, rxlist.com) found no copper-related mention for abaloparatide. Abaloparatide's pharmacokinetic profile (Step 1) gives no plausible mechanism either: it is a subcutaneously injected peptide with no gastrointestinal absorption step to chelate or compete at, no CYP450 involvement, and no known copper-cofactor dependency in its proteolytic clearance pathway. Access note: this specific query (PubMed search-listing page) returned a genuine, explicit zero-result page rather than a bot-verification block, so this is treated as a clean literature gap, not primarily a tooling limitation, though the session's broader rate-limiting (disclosed in the headline finding) means a deeper Europe PMC or Semantic Scholar cross-check could not be completed.

Iron

Not graded — disclosed evidence gap

See study details

No Tier B or C evidence, at either the abaloparatide-specific or the teriparatide/PTH-class level, and no circulating consumer claim, connecting abaloparatide to iron status (ferritin, transferrin saturation, serum iron) was found; the adjacent hematopoietic stem cell finding under Oxygen delivery/utilization does not measure iron status itself and was deliberately not used to support a grade here.

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded

Limits on what this shows

  • Why no grade: The dual condition for ungraded is met. A PubMed search-listing query for "abaloparatide iron" returned a confirmed, explicit zero-result page. The sibling teriparatide dossier independently reached the same ungraded conclusion for iron at the class level. A consumer-facing interactions/side-effects check (drugs.com, rxlist.com) found no iron-related mention for abaloparatide, and drugs.com's own "frequently checked together" interaction list for abaloparatide explicitly did not include iron. The hematopoietic stem cell mobilization finding under Oxygen delivery/utilization (class-extrapolated from teriparatide) concerns marrow progenitor activity, not ferritin, transferrin saturation, or other direct iron-status markers; using it here would double count one signal as two findings, so it was intentionally excluded from this entry (see Overlap map). Access note: this specific query returned a genuine, explicit zero-result page, treated as a clean literature gap rather than primarily a tooling limitation, though the session's broader rate-limiting means a deeper Europe PMC or Semantic Scholar cross-check could not be completed.

Gut Microbiome Risk

Each finding below is counted once, in this area only.

Gut microbiome risk, class extrapolation from a teriparatide-specific compositional study, protective direction, source not reopened this session

Yellow — Low

See study details

No abaloparatide study of any kind on gut microbiome composition was found; the sibling teriparatide dossier in this same batch independently found and cited a teriparatide-specific human study showing enrichment of beneficial bacterial genera, but that source could not be reopened and independently reverified during this abaloparatide-focused session, so it is graded yellow with that reliance explicitly disclosed.

Full detail and limits

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow

Limits on what this shows

  • Key negative/null findings: No diversity-loss or dysbiosis marker was reported for the teriparatide arm in the sibling dossier's characterization; the direction found was enrichment of beneficial taxa, not depletion.
  • At-risk subgroups: Not established for either drug.
  • Counter-evidence on record: Non-randomized, open-label design with no untreated control arm limits attribution for the underlying teriparatide finding itself, independent of the abaloparatide-extrapolation question; this entry carries both that limitation and the added, unverified cross-drug extrapolation.

Regulatory status

Not addressed in labeling.

Population evidence

Abaloparatide-specific: a PubMed search combining "abaloparatide" with "microbiome," "microbiota," and "gut bacteria" returned a confirmed zero-result count. Class-level, as cited and opened by the sibling teriparatide dossier produced under the same protocol earlier in this batch (not independently reopened by this reviewer this session; attempted once, blocked by a 429 rate-limit with an explicit "do not retry" instruction): Archives of Osteoporosis 2026, non-randomized open-label comparative study, 108 completers (68 teriparatide, 40 denosumab, both arms with concomitant calcium and vitamin D), 6 months, fecal 16S rDNA sequencing. Teriparatide significantly enriched the genera Dubosiella and Butyrivibrio, both short-chain-fatty-acid producers; Dubosiella abundance correlated positively with L4 and hip bone mineral density, Butyrivibrio with L2 bone mineral density.

Mechanism

Not fully elaborated in the source as characterized by the sibling dossier; framed there as linked to the drug's bone-anabolic, high-bone-turnover mechanism rather than to a gut-toxicity or absorption-interference pathway. Abaloparatide's route of administration (subcutaneous, complete gastrointestinal bypass) gives no direct mechanistic reason to expect gut-luminal contact with the drug itself, so any effect, if present, would have to be systemic/hormonal rather than local, an added uncertainty for extrapolating this specific compositional finding.

Counter-evidence held on record

This is a protective-direction, class-level finding not confirmed for abaloparatide and not independently reverified this session: it should never be presented as evidence of microbiome harm or benefit specific to abaloparatide, and should never be used to suggest probiotic supplementation is necessary.

Oxygen and ATP Output

Oxygen delivery and ATP production are assessed separately. Nothing here is counted twice.

Oxygen delivery/utilization, class extrapolation from a self-verified teriparatide cohort, stem-cell mobilization confirmed, red-cell effect null

Yellow — Low

See study details

No abaloparatide-specific oxygen-delivery or hematologic study could be opened this session; a self-verified, drug-specific teriparatide cohort found increased circulating hematopoietic stem cells with no red blood cell change, graded yellow here as class extrapolation only, alongside an abaloparatide-titled ischemia-reperfusion lead that could not be verified.

Full detail, limits and 2 references

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow

Limits on what this shows

  • Key negative/null findings: The Yu et al cohort's explicit finding of no significant red blood cell change is the most informative result available and is reported here as a genuine null for the oxygen-delivery question specifically, for teriparatide; it is not known whether this null extends to abaloparatide.
  • At-risk subgroups: Not established for either drug.
  • Counter-evidence on record: None found beyond the null red-cell finding itself; the entry's main limitation is that all direct human data is teriparatide-specific, not abaloparatide-specific.

Regulatory status

Not addressed in labeling for either drug.

Population evidence

Abaloparatide-specific: the same Wider et al 2022 title (PTHrP and abaloparatide attenuating myocardial ischemia-reperfusion injury) is directly relevant to this category by title (ischemia-reperfusion concerns tissue oxygen deprivation) but could not be opened and verified this session; not used as evidence here. A PubMed search combining "abaloparatide" with "hemoglobin," "hematocrit," or "erythropoiesis" returned a confirmed zero-result count. Class-level, self-verified by directly opening the full text this session: Yu et al, Journal of Bone and Mineral Research 2014 (PMC4564394). Prospective longitudinal trial, 23 postmenopausal women at high fracture risk (18 with baseline hematopoietic stem cell data), teriparatide 20 mcg SC daily for 24 months, flow cytometry at baseline, 3, 6, 12, 18, and 24 months. Peripheral hematopoietic stem cells increased 40%±14% by month 3 (P=.004), remained elevated at 6 months (P=.013) and 18 months (P=.044), returning to baseline by 24 months. Complete blood count showed no significant change in white cells, lymphocytes, neutrophils, monocytes, red blood cells, or platelets across the study.

Mechanism

Proposed but not fully established at the class level: PTH signaling is known to act on the bone marrow hematopoietic stem cell niche, plausibly mobilizing stem cells without necessarily changing mature red-cell output. Not tested for abaloparatide specifically.

Counter-evidence held on record

Do not present as an established anemia or oxygen-delivery risk or benefit for abaloparatide specifically; the best-powered human data found showed no red blood cell change, and it comes from a different (though closely related) drug. Anemia in an osteoporosis population has many causes; do not attribute any hemoglobin change to abaloparatide without excluding these.

ATP production, class extrapolation from teriparatide, glycolytic substrate-preference shift in osteoblasts, not a systemic or abaloparatide-verified finding

Yellow — Low

See study details

The same self-verified class-level review that supports the Mitochondrial burden entry describes PTH(1-34) shifting osteoblast ATP generation toward glycolysis during anabolic bone formation; no abaloparatide-specific ATP or energy-metabolism study of any kind was found.

Full detail, limits and 1 references

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow

Limits on what this shows

  • Key negative/null findings: No direct ATP-output or whole-body energy-expenditure measurement in teriparatide- or abaloparatide-treated humans or animals was found; a pathway-level substrate shift in one cell type in one PTH-axis drug is not the same as a systemic ATP-production claim for either drug, and this entry is written accordingly.
  • At-risk subgroups: Not applicable; cell-type-specific, class-level finding, not a patient subgroup risk.
  • Counter-evidence on record: None found; the gap is the absence of any direct systemic energetic measurement for either drug, and the complete absence of abaloparatide-specific data, not a contradicting result.

Regulatory status

Not addressed in labeling.

Population evidence

Abaloparatide-specific: a PubMed search combining "abaloparatide" with "ATP," "oxygen consumption," and "energy metabolism" returned a confirmed zero-result count. Class-level, same self-verified source as Mitochondrial burden (Journal of Bone and Mineral Research 2024 review, its reference 44, primary mouse study not independently opened): aerobic glycolysis activation with blocked TCA-cycle glucose entry in mouse osteoblasts under PTH(1-34) signaling, with the bone-anabolic effect abolished when glucose was pharmacologically forced back into oxidative metabolism.

Mechanism

Named at the class level: aerobic glycolysis substitutes for mitochondrial oxidative phosphorylation as the dominant ATP source in differentiating mouse osteoblasts during PTH(1-34)-driven anabolism; not tested for abaloparatide, and the same PTHrP-analog signaling-profile caveat applies.

Counter-evidence held on record

Do not present as evidence that abaloparatide increases or decreases whole-body cellular energy or causes fatigue; the source describes a substrate-preference shift within bone-forming cells in a related drug specifically, not confirmed for abaloparatide and not a systemic ATP deficit. Shares its underlying class-level source with the Mitochondrial burden entry above; see Overlap map.

Claims checked and not supported

These circulate online for this medication. They are listed here only so they can be answered, never as findings, and they are not graded.

A claim with no supporting evidence is not necessarily disproven. Where evidence actually argues against a claim, that is stated below.

  • Coenzyme Q10

    Where it comes from: Drugs.com's automated "most frequently checked interactions" list for abaloparatide names CoQ10 (ubiquinone) as a "moderate interaction," without describing any actual documented mechanism, echoing generic "drug mugging" style depletion lists built for mevalonate-pathway drugs (chiefly statins).

    Why it fails: Abaloparatide is a 34-amino-acid peptide administered subcutaneously and cleared by non-specific proteolysis; it does not act on the mevalonate/HMG-CoA reductase pathway or any other CoQ10 biosynthetic step, and has no gastrointestinal absorption step to interfere with co-administered CoQ10. No drug-specific or PTH-class study measuring CoQ10 status was found or opened during this review.

  • Vitamin B12

    Where it comes from: Drugs.com's automated "most frequently checked interactions" list for abaloparatide names vitamin B12 (cyanocobalamin) as a "moderate interaction," echoing depletion lists more legitimately built for acid-suppressing drugs (PPIs, H2 blockers) and metformin.

    Why it fails: Abaloparatide has no acid-suppression mechanism, no intrinsic-factor interference, and no metformin-like ileal-absorption mechanism; as a subcutaneous injection it bypasses the entire gastric-acid/intrinsic-factor/terminal-ileum B12 absorption pathway entirely. No drug-specific or PTH-class study measuring B12 status was found or opened during this review.

All references used above
  1. TYMLOS (abaloparatide) injection, for subcutaneous use, prescribing information. — DailyMed, U.S. National Library of Medicine; also accessdata.fda.gov label PDF (2024/208743Orig1s015lbl.pdf). Regulatory label, setid 712143d9-e21e-4013-bb3b-3426a21060a8. Used for pharmacokinetics, mechanism of action, calcium, phosphate/vitamin D, uric acid, renal impairment, and adverse-event data throughout.
  2. Cosman F, et al. Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis: A Randomized Clinical Trial (the ACTIVE trial). — JAMA, 2016. Randomized, double-blind, placebo- and teriparatide-controlled, n=2,463 women, 18 months, 28 sites/10 countries. Used for Calcium entry (hypercalcemia 3.4% abaloparatide vs 6.4% teriparatide) and Monitoring panel (orthostatic hypotension rate).
  3. Czerwinski E, et al. The Efficacy and Safety of Abaloparatide-SC in Men With Osteoporosis: A Randomized Clinical Trial (the ATOM trial). — Journal of Clinical Endocrinology and Metabolism, 2022. Randomized, double-blind, placebo-controlled, n=228 men, 12 months. PMC10091818. Used for Calcium and Uric acid entries (men's-trial figures) and Monitoring panel.
  4. Yang Y, Tseng WJ, Wang B. Abaloparatide Maintains Normal Rat Blood Calcium Level in Part Via 1,25-Dihydroxyvitamin D/osteocalcin Signaling Pathway. — Endocrinology, 2023;164(9):bqad117. Intact male Sprague-Dawley rats, n=8, abaloparatide 40 mcg/kg/day SC, 7 days, versus vehicle. Used for Calcium and Phosphate/vitamin D axis entries.
  5. Wider J, Undyala VVR, Lanske B, Datta NS, Przyklenk K. Parathyroid Hormone-Related Peptide and Its Analog, Abaloparatide, Attenuate Lethal Myocardial Ischemia-Reperfusion Injury. — Journal of Clinical Medicine, 2022;11(9):2596. PMID 35566399. Title and citation confirmed via a PubMed search-listing page; directly relevant to Mitochondrial burden, Oxidative stress, and Oxygen delivery/utilization by title, but the abstract and full text could not be opened during this review.Could not be opened: the individual PubMed abstract page returned a reCAPTCHA bot-verification challenge on every attempt (retried after 30, 45, 60, and 90-second waits); a guessed MDPI DOI (10.3390/jcm11092596) resolved to an unrelated article (confirmed via doi.org redirect, then fetched and found to be about myelodysplastic syndromes, not this paper), so no substitute full-text URL could be found; Europe PMC, Semantic Scholar, Crossref, OpenAlex, and scholar.archive.org all returned repeated 429 rate-limit responses or explicit "do not retry" instructions for this and related queries; NCBI eutils and PMC's own search-listing pages returned robots.txt disallowals. Listed here for a future revision to re-check; not used as supporting evidence anywhere in this dossier.
  6. Yu EW, Kumbla NA, Mikulec KH, et al. Teriparatide (PTH 1-34) Treatment Increases Peripheral Hematopoietic Stem Cells in Postmenopausal Women. — Journal of Bone and Mineral Research, 2014;29(6):1380-1386. Prospective longitudinal trial, n=23 (18 with longitudinal HSC data), teriparatide 20 mcg/day SC, 24 months. PMC4564394. Teriparatide-specific; used only as class-level (Tier C) extrapolation for the Oxygen delivery/utilization entry, independently opened and read during this abaloparatide review.
  7. Role of Teriparatide in Glucocorticoid-induced Osteoporosis through Regulating Cellular Reactive Oxygen Species. — In vitro (MLO-Y4 osteocytes, teriparatide 10 nmol/L) and in vivo (Sprague-Dawley rats, n=20, dexamethasone-induced osteoporosis model) study. PMC6594530. Teriparatide-specific; used only as class-level (Tier C) extrapolation for the Oxidative stress entry, independently opened and read during this abaloparatide review.
  8. Teriparatide mitigates oxidative stress following spinal cord injury and enhances neurological recovery via the Nrf2/HO-1 signaling pathway. — Frontiers in Pharmacology, 2025. In vivo rat study, n=138, teriparatide 20 mcg/kg/day SC, 14 days. Teriparatide-specific; used only as class-level (Tier C) extrapolation for the Oxidative stress entry, independently opened and read during this abaloparatide review.
  9. Multifaceted roles of mitochondria in osteoblasts: from energy production to mitochondrial-derived vesicle secretion. — Journal of Bone and Mineral Research, 2024. Narrative review; characterizes a mouse osteoblast PTH(1-34) aerobic-glycolysis study (cited within as its reference 44, not independently opened). Teriparatide-specific; used only as class-level (Tier C) extrapolation for the Mitochondrial burden and ATP production entries, independently opened and read during this abaloparatide review.
  10. A clinical study on the effects of teriparatide and denosumab on bone metabolism and gut microbiota in osteoporotic fracture patients. — Archives of Osteoporosis, 2026. Non-randomized, open-label, comparative study, n=108 (68 teriparatide, 40 denosumab), 6 months, 16S rDNA fecal sequencing. Teriparatide-specific; used only as class-level (Tier C) extrapolation for the Gut microbiome risk entry, as characterized by the sibling teriparatide dossier in this same batch.Not independently reopened during this abaloparatide-focused session: one retry attempt returned an HTTP 429 rate-limit response. This entry relies on the sibling teriparatide dossier's own citation of this source, disclosed in the Gut microbiome risk entry rather than presented as independently reverified.
  11. NCBI Bookshelf, physiology reference on parathyroid hormone renal actions. — Quoted directly: "Circulating parathyroid hormone targets the distal convoluted tubule and collecting duct, directly increasing calcium reabsorption" and "Parathyroid hormone decreases phosphate reabsorption at the proximal convoluted tubule." Used for the named mechanism in the Calcium and Phosphate/vitamin D axis entries.
  12. Tymlos side effects (professional). — Drugs.com. Consumer/professional side-effects reference; checked for magnesium, phosphate, vitamin D, antioxidant, mitochondrial, and energy-related claims (none found beyond hypercalcemia/hypercalciuria symptoms) and for the hypercalciuria percentage cited in the Monitoring panel.
  13. Tymlos (abaloparatide) drug information. — RxList. Consumer reference; cross-checked label figures (uric acid, phosphate, calcium/vitamin D supplementation range) and confirmed no magnesium, iron, copper, gut microbiome, or mitochondrial/energy claims are circulating for abaloparatide on this source.
  14. Abaloparatide interactions checker. — Drugs.com. Consumer "most frequently checked interactions" listing; used to identify Vitamin D3, Vitamin B12, CoQ10, fish oil, and flax seed oil as commonly co-searched items with no described mechanism given, supporting the Fails verification entries (CoQ10, Vitamin B12) and confirming calcium, magnesium, zinc, and iron are notably absent from this list.
  15. Abaloparatide. — Wikipedia. Used only for the ATC code (H05AA04) and brand names (Tymlos, Eladynos), both cross-checked against the label and DailyMed for the mechanism-of-action and adverse-event content used elsewhere in this dossier.
  16. PubMed search-listing queries: "abaloparatide copper," "abaloparatide iron," "abaloparatide microbiome OR microbiota OR gut bacteria," "abaloparatide hemoglobin OR hematocrit OR erythropoiesis," "abaloparatide ATP OR oxygen consumption OR energy metabolism," "abaloparatide mitochondria OR oxidative stress." — pubmed.ncbi.nlm.nih.gov search-listing pages (not individual abstract pages), each fetched and read directly, each returning either a confirmed explicit zero-result page or the single Wider et al 2022 title. Used to establish the Ungraded entries (Copper, Iron) and the genuine-versus-tooling-limited distinction described in the headline finding.
  17. Europe PMC REST API, Semantic Scholar Graph API, Crossref API, OpenAlex API, Unpaywall search, NCBI eutils, PMC search-listing pages, scholar.archive.org, individual PubMed abstract pages. — Attempted repeatedly across this session for abaloparatide-specific mitochondrial, oxidative-stress, and oxygen-delivery queries. Not a citable study; recorded here for audit transparency per the Step 4 thoroughness requirement.Could not be used: persistent HTTP 429 rate-limiting (several explicitly instructing no further retries), robots.txt disallowals, or reCAPTCHA bot-verification challenges, spread across more than a dozen attempts with 30-90 second waits between them late in this session.