**5.3 Anabolic conventional therapies**

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 ultimately osteoporosis precipitation [28].

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 hyperparathyroidism [31].

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 resorption [32].

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*,


**Table 2.**

**93**

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

OVX mice [35].

spinal implants [41–44].

efficacy and patient compliance.

**6. Conclusion**

and so on, which have proven reported results in various animal models on improving bone health [33, 34]. Reports suggest the fact that Hachimi-jio-gan and Juzen-taiho-to significantly prevented the loss of bone in SAMP6, a murine model for senile osteoporosis [34]. The decoction containing Bushenningxin caused osteoblasts to have an increase in the number of cell organelles with clear Golgi apparatus, increased proliferation, and inhibition of apoptosis for a time period of 12 weeks when given to

Recent advances in MBD treatment include medications that target calciumsensing receptors and proteins linked to the hormone parathyroid, leading to the design of cathepsin K and Src tyrosine kinase inhibitors, calcilytics, and monoclo-

Nanoenabled systems for the systemic delivery of drugs for the treatment of MBD have attracted huge attention in recent times. A number of formulations were designed for the controlled delivery of medicaments for better therapeutic efficacy with minimal associated adverse effects. Some of the formulations reported in this specified category include tigecycline entrapped calcium phosphate/poly-DLlactide-co-glycolide nanoparticles, titanium implants coated with bisphosphonate encased calcium phosphate nanoparticle, and gold nanoparticles incorporated gelatin-based hydrogel. Reports suggest that surface reconfiguration through nanotechnology has played a significant role in the design and manufacture of better

The burgeoning of the incidences of MBD is raising concern worldwide. Proper

screening of the disorder is of prime importance in dealing with it. Although bisphosphonates remain the first-line treatment choice for the stated disorder, researchers should work upon the novel drugs with a unique mode of action and appreciable long-term safety profile. Based on the literature, it is pertinent to state that a fine balance between the non-pharmacological and pharmacological approaches could help out in dealing with MBD judiciously resulting in its prevention. Therefore, the battle for the search of better drugs for treating patients with metabolic bone diseases continues with an aim to provide better therapeutic

nal antibodies against sclerostin or Dickkopf-1 (**Table 2**).

*Recent advances for the treatment of metabolic bone disease.*

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

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

**92**

**Class of drug**

Calcilytics Cathepsin K

ODN ONO-5334

Synthetic derivative,

low molecular weight,

oral formulation

Src tyrosine kinase

Saracatinib

Oral formulation

Inhibits the

enzyme Src kinase

competitively

(AZD0530)

inhibitors

Monoclonal

Romosozumab

Human monoclonal

Monoclonal antibody

against sclerostin

anti-sclerostin antibody

*PTH, parathyroid hormone; CaSR, calcium sensing receptor; BMD, bone mineral density; CatK, cathepsin K.*

(AMG-785)

antibodies against

sclerostin/

Dickkopf-1

**Table 2.**

*Recent advances for the treatment of metabolic bone disease.*

Long half-life, orally

Inhibits CatK

from binding to

its corresponding

substrates

Inhibits CatK

In Phase 2 clinical trial in postmenopausal women with osteoporosis,

[38]

there was a substantial enhancement in BMD in the lumbar spine, total

hip, and femoral neck compared to placebo. The observed effect on BMD

of ONO-5334 was found to have a similar effect as that of alendronate,

when administered at a dose of 70 mg once weekly

A notable decrease in bone resorption markers without any noticeable

[39]

effect on bone formation markers and no serious adverse effects was

documented, demonstrating a reduction in osteoclast bone resorption

A rise in dose-dependent BMD at the lumbar spine and total hip with a

[40]

decrease in bone resorption markers with marked improvement in bone

formation markers after a period of 3 months was reported

effect of saracatinib

from binding to

its corresponding

substrates

bioavailable

inhibitors

MK-5442 (Phase

Orally bioavailable

CaSR antagonist

II)

**Investigational** 

**Characteristics**

**Mode of action**

**Therapeutic efficacy**

Transient PTH pulses and a dramatic rise in the formation of bone

markers were noted, with a transitory significant decline in markers

of bone resorption. Compared to placebo, no further rise in BMD was

Reduced bone turnover in ovariectomized animals and promoted

[37]

periosteal bone formation was observed

reported

**References**

[36]

**drug**

and so on, which have proven reported results in various animal models on improving bone health [33, 34]. Reports suggest the fact that Hachimi-jio-gan and Juzen-taiho-to significantly prevented the loss of bone in SAMP6, a murine model for senile osteoporosis [34]. The decoction containing Bushenningxin caused osteoblasts to have an increase in the number of cell organelles with clear Golgi apparatus, increased proliferation, and inhibition of apoptosis for a time period of 12 weeks when given to OVX mice [35].

Recent advances in MBD treatment include medications that target calciumsensing receptors and proteins linked to the hormone parathyroid, leading to the design of cathepsin K and Src tyrosine kinase inhibitors, calcilytics, and monoclonal antibodies against sclerostin or Dickkopf-1 (**Table 2**).

Nanoenabled systems for the systemic delivery of drugs for the treatment of MBD have attracted huge attention in recent times. A number of formulations were designed for the controlled delivery of medicaments for better therapeutic efficacy with minimal associated adverse effects. Some of the formulations reported in this specified category include tigecycline entrapped calcium phosphate/poly-DLlactide-co-glycolide nanoparticles, titanium implants coated with bisphosphonate encased calcium phosphate nanoparticle, and gold nanoparticles incorporated gelatin-based hydrogel. Reports suggest that surface reconfiguration through nanotechnology has played a significant role in the design and manufacture of better spinal implants [41–44].
