What Is The Impact Of Parathyroid Hormone On Bone Remodeling?

Parathyroid hormone (PTH) plays a crucial role in skeletal homeostasis through multiple cellular and molecular mechanisms. It enhances the number and activation of osteoblasts through four pathways: increasing osteoblast proliferation and differentiation, decreasing osteoblast apoptosis, and reducing the negative effects of peroxisome proliferator activator (PPAR)γ receptor on osteoblast differentiation. PTH stimulates bone remodeling by modulating the synthesis of critical proosteoclastogenic factors, mainly RANKL, and the level of calcium. Studies in animal models and humans have shown that PTH administration leads to increased bone formation through an increase in osteoblast number and surface, as well as an increase in mineralized matrix deposition through effects on proliferation of precursors, suppression of apoptosis, and activation of lining cells.

PTH is essential for maintaining calcium homeostasis through its actions to regulate bone remodeling. In the bone, PTH increases bone remodeling through its actions on osteoblasts and osteoclasts. It directly stimulates osteoblasts to increase bone formation. Intermittent treatment with parathyroid hormone increases bone formation in adult rats by activating bone lining cells.

PTH stimulates bone remodeling and may cause bone loss or gain depending on the balance between bone resorption and formation. High-frequency dosage schemes accelerate bone turnover featuring remodeling-based bone formation, while low-frequency administration has a stimulatory effect on bone resorption and upregulates bone turnover. However, the responsiveness of bone to PTH varies widely. In adults, elevated PTH is associated with increased rates of bone breakdown and formation, thus resulting in weaker bones.

In conclusion, PTH plays a significant role in skeletal homeostasis through various cellular and molecular mechanisms. Its paradoxical and therapeutic effect on bone formation is attributed to its integration with calcitonin and vitamin D active forms.

How does parathyroid hormones affect bones?

Parathyroid hormone is a hormone that regulates calcium levels in the body. It is released from large calcium stores in bones, which increases bone destruction and decreases new bone formation. It also reduces calcium loss in urine and stimulates the production of active vitamin D in the kidneys. In the intestine, it indirectly increases calcium absorption through vitamin D metabolism. Parathyroid hormone is controlled by the negative feedback of calcium levels in the blood to the parathyroid glands.

High calcium levels stimulate parathyroid hormone secretion, while low levels prevent it. Overproduction of parathyroid hormone can lead to hypercalcaemia, a primary issue in the parathyroid glands. Tertiary hyperparathyroidism occurs due to excess parathyroid hormone production on the back drop of all four overactive glands. Secondary hyperparathyroidism occurs in response to low blood calcium levels and is caused by other mechanisms, such as kidney disease and vitamin D deficiency.

What is the function of the parathyroid gland in the bones?

The parathyroid glands maintain serum calcium homeostasis by synthesizing and releasing PTH. PTH inhibits osteoblast activity and stimulates osteoclast activity, leading to bone breakdown and calcium release. It increases calcium reabsorption at the kidneys and blocks phosphate reabsorption from tubules. PTH also stimulates vitamin D formation in the kidneys, which is essential for calcium and phosphate homeostasis.

PTH indirectly stimulates osteoclasts to break down bone by binding to cell receptors on osteoblasts, stimulating the release of Receptor Activator of Nuclear factor Kappa-B Ligand (RANKL). This stimulates osteoclast precursors to fuse into mature osteoclasts, increasing calcium resorption from bone.

PTH plays two main roles in the kidney: increasing calcium reabsorption by up-regulating TRPV5, a calcium transporter on the tubular epithelium, and blocking phosphate reabsorption in the proximal tubule. It also works at the kidneys to up-regulate the translation of alpha-1-hydroxylase, the enzyme responsible for generating vitamin D. Vitamin D binds to bone receptors, increasing serum calcium and phosphate reabsorption in the kidney.

How would parathyroid hormone affect osteoclasts?

PTH receptor signaling in osteoblasts and osteocytes can increase the RANKL/OPG ratio, enhancing osteoclast recruitment and activity, and stimulating bone resorption. This is supported by two recent papers: Hanley et al.’s study on the pharmacological mechanisms of therapeutics with parathyroid hormone and Civitelli et al.’s study on calcium and phosphate homeostasis, both published within the review period.

Is bone remodeling controlled by parathyroid hormone?

PTH stimulates bone remodeling, but bone resorption is more prevalent when exposed to high levels. Low, intermittent doses of PTH lead to a net increase in bone mass. Two papers of interest, “Pharmacological mechanisms of therapeutics: parathyroid hormone” and “Calcium and phosphate homeostasis: concerted interplay of new regulators”, provide insights into the pharmacological mechanisms of therapeutics and the interplay of new regulators in bone remodeling and homeostasis.

What is the action of parathyroid hormone on bone tissue?

Parathyroid hormone (PTH) stimulates bone resorption by acting directly on osteoblasts/stromal cells and indirectly increasing the differentiation and function of osteoclasts. PTH acts on these cells by increasing collagenase gene transcription and synthesis. To assess the role of collagenase in the bone resorptive actions of PTH, mice homozygous for a targeted mutation in Col1a1 were used. Human PTH was injected subcutaneously over the hemicalvariae in wild-type (+/+) or r/r mice four times daily for three days.

Osteoclast numbers, the size of the bone marrow spaces, and periosteal proliferation were increased in calvariae from PTH-treated +/+ mice, whereas in r/r mice, PTH-induced bone resorption responses were minimal.

The study found that collagenase cleavage of type I collagen is necessary for PTH induction of osteoclastic bone resorption. PTH induces hypercalcemia in part through increasing bone resorption mediated by osteoclasts. Receptors for PTH are present not on osteoclasts but on mesenchymal cells of the osteoblast lineage and stromal cells in the bone marrow. PTH must act directly on these mesenchymal cells, which then modulate the activity of existing osteoclasts and the differentiation of osteoclasts from precursor cells.

Collagenase activity was found to be higher in bones removed from mice injected with doses sufficient to elevate serum calcium levels by ∼4 mg/dl. The sustained hypercalcemia induced by PTH was obviated by inhibitors of mRNA synthesis (actinomycin D) or protein synthesis (puromycin), suggesting that at least in part, PTH-induced hypercalcemia is dependent upon the synthesis of a protein in bone, such as collagenase.

Osteoclasts produce cysteine proteinases and matrix metalloproteinase-1 (MMP-1) in humans. However, it has been difficult to identify the expression of specific collagenases in osteoclasts using cDNA or cRNA probes. When exposed to PTH, osteoblasts start producing collagenase and stop synthesizing collagen.

What is the mechanism of action of parathyroid hormone treatment osteoporosis?

PTH induces hypercalcemia by increasing bone turnover, which may mobilize skeletal calcium stores, and increasing renal production of 1, 25-dihydroxyvitamin D, which increases gastrointestinal absorption and renal tubular reabsorption of calcium. At the Fracture Prevention Trial (FPT), hypercalcemia was observed in 11 patients administered 20 mcg/day teriparatide, and consecutive hypercalcemia was observed in 3 patients. The FDA has no recommendation for monitoring serum calcium in these patients, but questions should be considered.

Serum calcium should be checked at least once in the first month after starting the therapy, and if hypercalcemia occurs, calcium intake could be reduced or stopped teriparatide and rechecked in 7 to 10 days. Hypercalciuria has a small risk of occurrence, and decisions regarding teriparatide effects on urinary calcium excretion must be interpreted in the context of the total clinical picture. Monitoring calcium excretion is not recommended in patients with no renal stones or normal basal urinary calcium.

In the FPT, serum uric acid increased above the upper limit of normal without any incidence of gout, and there is no guidance regarding management of patients with uric acid disorders. Clinical judgment must prevail.

What does the parathyroid hormone do?

The parathyroid hormone, produced by two pairs of small, oval-shaped glands located next to the thyroid gland lobes in the neck, plays a crucial role in regulating calcium levels in the blood. It stimulates the release of calcium by bones into the bloodstream, absorption of calcium from food by the intestines, and conservation of calcium by the kidneys. The precise calcium levels are essential for the human body to prevent muscle and nerve problems.

Which hormone is responsible for bone remodeling?

Osteoclasts play a crucial role in bone remodeling and resorption, while osteoblasts lay down new bone. Two hormones that affect osteoclasts are parathyroid hormone (PTH) and calcitonin. PTH stimulates osteoclast proliferation, releasing calcium into the bloodstream and promoting calcium reabsorption by kidney tubules, which can affect calcium homeostasis. PTH indirectly affects the small intestine by stimulating vitamin D synthesis, which promotes calcium absorption.

Calcitonin, secreted by the thyroid gland, inhibits osteoclast activity and stimulates calcium uptake by bones, reducing calcium ion concentration in the blood. PTH and calcitonin are generally not secreted simultaneously, as they have opposing functions in maintaining calcium homeostasis.

How does calcitonin affect bone remodeling?

Calcitonin is a hormone that regulates calcium levels in the body, affecting the kidneys’ ability to reabsorb calcium from the bone. It temporarily blocks the activity of osteoclasts, which break down bone, reducing the amount of calcium that enters the bloodstream. The thyroid releases calcitonin based on the level of calcium in the blood, with higher levels indicating higher calcitonin release and lower levels indicating lower calcitonin release. Both parathyroid hormone and calcitonin play a role in regulating calcium levels, but their impact on calcium levels is different.

Which hormone inhibits bone growth?

Cortisol, a hormone from the adrenal gland, plays a crucial role in metabolism and the body’s response to stress and injury. It has complex effects on the skeleton, with small amounts necessary for normal bone development and large amounts blocking growth. Synthetic forms of cortisol, called glucocorticoids, are used to treat diseases like asthma and arthritis. However, they can cause bone loss due to decreased bone formation and increased bone breakdown, leading to a high risk of fracture.

Insulin is also important for bone growth, and individuals with insulin deficiency may have impaired response to other factors that stimulate bone growth. Leptin, a hormone from fat cells, has also been shown to affect bone. Maintaining a strong and healthy skeleton requires the right amount of bone with the right structure and composition in the right place.

What are the three effects of the parathyroid hormone?

The parathyroid hormone, produced by two pairs of small, oval-shaped glands located next to the thyroid gland lobes in the neck, plays a crucial role in regulating calcium levels in the blood. It stimulates the release of calcium by bones into the bloodstream, absorption of calcium from food by the intestines, and conservation of calcium by the kidneys. The precise calcium levels are essential for the human body to prevent muscle and nerve problems.