**5. Treatment approaches for MBD**

The recent decade has witnessed much progress in the introduction of new medications for the treatment of MBD. The treatment modality of this group of disorders comprises two major treatment regimens, antiresorptive and anabolic conventional therapies. Antiresorptive drugs predominantly reduce the bone resorption rate, while anabolic drugs boost the formation of bone. The following medicines for skeletal disorders, including Paget's disease of the bone, osteoporosis, MBD, and several other rare type of bone diseases, form the basis of our current clinical treatment regimen.

#### **5.1 Antiresorptive agents**

The major class of drugs included in this category includes bisphosphonates, estrogens, calcitonin, and denosumab.

Bisphosphonates, first-line antiresorptive bone agents, are commonly used to treat osteoporosis caused by glucocorticoids and other disorders marked by severe osteoclastic bone resorption, such as humoral malignant hypercalcemia, Paget's disease, multiple myeloma, and osteolytic bone metastasis [22]. The drugs specifically included in this group for the treatment of MBD comprises of alendronate, risedronate, and zoledronic acid. Such groups of therapeutic agents bind with a high affinity to the bone's mineral matrix and prevent resorption of osteoclast of the bone, resulting in reduced bone turnover and a significant increase in bone mass [23]. The most prominent side effect related to bisphosphonates administered orally is the upper gastrointestinal discomfort, which majorly includes the erosion of the esophagus leading to ulcer, heartburn, and indigestion.

Calcitonin is approved for the treatment of osteoporosis care in postmenopausal women when alternative therapies are not practicable [24].

Denosumab, the first biological agent available for osteoporosis treatment, is a fully human monoclonal antibody that acts by inhibiting transmembrane protein (RANKL), which has proven results for the formation and functioning of osteoclasts, thereby reducing bone resorption. It is usually recommended for the patients who are unable to be on drug therapy, which are orally administered

**91**

thyroidism [31].

resorption [32].

*Calcium and Metabolic Bone Disorders DOI: http://dx.doi.org/10.5772/intechopen.92977*

**5.2 Estrogen agonist/antagonist**

treatment [25, 26].

but are at high risk for the incidence of fractures. Denosumab is well-tolerated, but associated hypersensitivity or dermatological reactions, musculoskeletal pain, infections, and hypercholesterolemia are the major documented adverse effects. It can trigger hypocalcemia, so calcium levels should be fixed before starting

Estrogen therapy is FDA approved exclusively for the prevention of osteoporosis in postmenopausal women who are at high risk, and should only be used when nonestrogenic osteoporotic medications have been deemed inappropriate. Hormonal replacement therapy is no longer recommended as a first choice for treating and preventing osteoporosis in postmenopausal and premenopausal women due to the

While antiresorptive drugs usually display a lower incidence of associated side effects, bone turnover suppression can elucidate the necrosis of the jaw and the incidence of atypical femur fractures that can be documented in patients with long-term bisphosphonate usage [27]. Because antiresorptive agents are unable to preserve bone mass and bone integrity, it continues to be of core interest to identify molecular targets that would promote osteoblast activity and lead to enhanced bone

Osteoanabolics are another category of drugs, which covers the PTH and parathyroid hormone-related peptide analogs. PTH functions as an efficient endocrine regulator for the maintenance of calcium and phosphate concentrations in extracellular space, vital to the preservation of concentration of calcium in serum and urinary samples within the normal physiological limit. High PTH levels lead to a high bone-turning state with bone resorption exceeding bone formation and

Teriparatide was the first anabolic treatment option approved for the treatment of osteoporosis, which has a mode of action similar to that of the PTH hormone. This works by triggering the development of new bone by increasing osteoblastic development when given in low doses [29]. In patients with Paget's bone disease, elevated concentrations of alkaline phosphatase, prior skeletal radiotherapy, recurrent or metastatic bone malignancy, hypercalcemic disorders such as primary hyperparathyroidism, avoidance of the treatment is suggested [30]. Abaloparatide is another FDA approved drug for the treatment of osteoporosis in postmenopausal women. It is further advised to avoid the treatment in patients with preexisting hypercalcemia and disorder such as primary hyperpara-

Another promising investigational drug is romosozumab, which is a sclerostin-neutralizing antibody. Reports have shown elsewhere that it is better alternative bisphosphonate alendronate in women with severe osteoporosis for reducing the risk of prominent clinical fractures. This was accompanied by a boost in bone formation markers with a decline in bone resorption markers, implying the action of both stimulating bone formation and inhibiting bone

Apart from these two major classes of drugs, various herbal medicines are also gaining attention for being used in the treatment of MBD. Some of them include Hachimi-jio-gan and Juzen-taiho-to, *Kami-kihi-to*, *Bushenningxin*, *Shu Di Shan Zha*,

overall associated health risks that hugely outweigh the benefits.

mass with reconstructed skeletal architectures.

**5.3 Anabolic conventional therapies**

ultimately osteoporosis precipitation [28].

#### *Calcium and Metabolic Bone Disorders DOI: http://dx.doi.org/10.5772/intechopen.92977*

*Mineral Deficiencies - Electrolyte Disturbances, Genes, Diet and Disease Interface*

regimens to end up in a conclusive remark [19].

The recommended protein intake is 0.8 g/kg/day [20].

**4.3 Adequate protein intake**

**4.4 Reducing the intake of caffeine**

restrict the intake of caffeine [21].

clinical treatment regimen.

**5.1 Antiresorptive agents**

estrogens, calcitonin, and denosumab.

**5. Treatment approaches for MBD**

the study setting, i.e., institution versus community dwellers. The risk of fracture among older adults was lower in the community dwellers than for institutionalized elderly people. However, further research is required for appropriate dose and dosing

Maintaining an appropriate intake of proteins is vital for maintaining musculoskeletal functioning in postmenopausal women and men over the age of 50 years.

The impact of various caffeinated beverages has been inferred as a trigger of osteoporosis and fragility fracture in individuals; hence, it is recommended to

The recent decade has witnessed much progress in the introduction of new medications for the treatment of MBD. The treatment modality of this group of disorders comprises two major treatment regimens, antiresorptive and anabolic conventional therapies. Antiresorptive drugs predominantly reduce the bone resorption rate, while anabolic drugs boost the formation of bone. The following medicines for skeletal disorders, including Paget's disease of the bone, osteoporosis, MBD, and several other rare type of bone diseases, form the basis of our current

The major class of drugs included in this category includes bisphosphonates,

Bisphosphonates, first-line antiresorptive bone agents, are commonly used to treat osteoporosis caused by glucocorticoids and other disorders marked by severe osteoclastic bone resorption, such as humoral malignant hypercalcemia, Paget's disease, multiple myeloma, and osteolytic bone metastasis [22]. The drugs specifically included in this group for the treatment of MBD comprises of alendronate, risedronate, and zoledronic acid. Such groups of therapeutic agents bind with a high affinity to the bone's mineral matrix and prevent resorption of osteoclast of the bone, resulting in reduced bone turnover and a significant increase in bone mass [23]. The most prominent side effect related to bisphosphonates administered orally is the upper gastrointestinal discomfort, which majorly includes the erosion of the esophagus leading to ulcer, heartburn, and

Calcitonin is approved for the treatment of osteoporosis care in postmenopausal

Denosumab, the first biological agent available for osteoporosis treatment, is a fully human monoclonal antibody that acts by inhibiting transmembrane protein (RANKL), which has proven results for the formation and functioning of osteoclasts, thereby reducing bone resorption. It is usually recommended for the patients who are unable to be on drug therapy, which are orally administered

women when alternative therapies are not practicable [24].

**90**

indigestion.

but are at high risk for the incidence of fractures. Denosumab is well-tolerated, but associated hypersensitivity or dermatological reactions, musculoskeletal pain, infections, and hypercholesterolemia are the major documented adverse effects. It can trigger hypocalcemia, so calcium levels should be fixed before starting treatment [25, 26].

## **5.2 Estrogen agonist/antagonist**

Estrogen therapy is FDA approved exclusively for the prevention of osteoporosis in postmenopausal women who are at high risk, and should only be used when nonestrogenic osteoporotic medications have been deemed inappropriate. Hormonal replacement therapy is no longer recommended as a first choice for treating and preventing osteoporosis in postmenopausal and premenopausal women due to the overall associated health risks that hugely outweigh the benefits.

While antiresorptive drugs usually display a lower incidence of associated side effects, bone turnover suppression can elucidate the necrosis of the jaw and the incidence of atypical femur fractures that can be documented in patients with long-term bisphosphonate usage [27]. Because antiresorptive agents are unable to preserve bone mass and bone integrity, it continues to be of core interest to identify molecular targets that would promote osteoblast activity and lead to enhanced bone mass with reconstructed skeletal architectures.
